Title

Title: Genetic relations to Pharmacogenetics and Epilepsy
Author: Giri Movva
Introduction:
Epilepsy is a neurological disorder that affects a variety of individuals. Epilepsy is a phenomenon of two or more unprovoked seizures ensuing neurochemical changes in the brain ADDIN EN.CITE <EndNote><Cite><Author>Cotter</Author><Year>2017</Year><RecNum>20</RecNum><DisplayText>1</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936713″>20</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Cotter, D.</author><author>Kelso, A.</author><author>Neligan, A.</author></authors></contributors><auth-address>Queen Mary, University of London, London, UK; Centre for Mind and Brain, University of California Davis, Davis, CA, USA. Queen Mary, University of London, London, UK; Royal London Hospital, London, UK. Queen Mary, University of London, London, UK; Homerton University Hospital, London, UK. Electronic address: [email protected]</auth-address><titles><title>Genetic biomarkers of posttraumatic epilepsy: A systematic review</title><secondary-title>Seizure</secondary-title><alt-title>Seizure</alt-title></titles><periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></periodical><alt-periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></alt-periodical><pages>53-58</pages><volume>46</volume><edition>2017/03/01</edition><keywords><keyword>Epilepsy, Post-Traumatic/*genetics</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Genetic biomarkers</keyword><keyword>Posttraumatic epilepsy</keyword><keyword>Traumatic brain injury</keyword></keywords><dates><year>2017</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1059-1311</isbn><accession-num>28242442</accession-num><urls><related-urls><url>https://www.seizure-journal.com/article/S1059-1311(17)30097-3/pdf</url></related-urls></urls><electronic-resource-num>10.1016/j.seizure.2017.02.002</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>1. Epilepsy is known to affect about 60 million people around the world, and it is the second most typical neurological disorder ADDIN EN.CITE <EndNote><Cite><Author>Zhi</Author><Year>2018</Year><RecNum>3</RecNum><DisplayText>2</DisplayText><record><rec-number>3</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524931914″>3</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Zhi, H.</author><author>Wu, C.</author><author>Yang, Z.</author></authors></contributors><auth-address>Department of Neurology, Zhejiang University of Traditional Chinese Medicine Affiliated Wenzhou Hospital, Wenzhou, Zhejiang, China. Department of Emergency, Huzhou Hospital of Traditional Chinese Medicine, Huzhou, Zhejiang, China. Department of Rehabilitation Medicine, Hospital of integrated Traditional Chinese and Western Medicine in Xiacheng District of Hangzhou City, Hangzhou, Zhejiang, China. Electronic address: [email protected]</auth-address><titles><title>SCN1A rs3812718 polymorphism is associated with epilepsy: An updated meta-analysis</title><secondary-title>Epilepsy Res</secondary-title><alt-title>Epilepsy research</alt-title></titles><periodical><full-title>Epilepsy Res</full-title><abbr-1>Epilepsy research</abbr-1></periodical><alt-periodical><full-title>Epilepsy Res</full-title><abbr-1>Epilepsy research</abbr-1></alt-periodical><pages>81-87</pages><volume>142</volume><edition>2018/04/02</edition><keywords><keyword>Epilepsy</keyword><keyword>Meta-analysis</keyword><keyword>Scn1a</keyword><keyword>rs3812718</keyword></keywords><dates><year>2018</year><pub-dates><date>May</date></pub-dates></dates><isbn>0920-1211</isbn><accession-num>29605548</accession-num><urls></urls><electronic-resource-num>10.1016/j.eplepsyres.2018.03.016</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>2. Epilepsy can affect anyone from a child to an adult. Various genes have been correlated to the susceptibility of epilepsy. Some of these genes are more susceptible to specific subcategories of epilepsy such as Dravet syndrome, which is a type of infantile epilepsy, post-traumatic epilepsy (PTE), etc.PEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZWlzbGVyPC9BdXRob3I+PFllYXI+MjAxNjwvWWVhcj48
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ADDIN EN.CITE.DATA 3-5. Pharmacoresistance related with epilepsy has been emerging in the research field. Anti-epileptic drugs are used to treat epilepsy, and some of the approved drugs are carbamazepine, phenytoin, valproic acid, and phenobarbital. About 20% of patients don’t respond to standardized treatmentsPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NYXJnYXJpPC9BdXRob3I+PFllYXI+MjAxODwvWWVhcj48
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ADDIN EN.CITE.DATA 6.

The most common genes that are correlated with epilepsy are SCN1A, SCN2A, SCN3A, SCN8A, and SCN9APEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CZXJnaHVpczwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+
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ADDIN EN.CITE.DATA 7, 11, 13. The voltage gated-sodium channels are essential because they participate in initiating and firing action potentials. SCN1A gene was one of the first ones identified to be related to epilepsy ADDIN EN.CITE ;EndNote;;Cite;;Author;Meisler;/Author;;Year;2010;/Year;;RecNum;19;/RecNum;;DisplayText;10;/DisplayText;;record;;rec-number;19;/rec-number;;foreign-keys;;key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936696″;19;/key;;/foreign-keys;;ref-type name=”Journal Article”;17;/ref-type;;contributors;;authors;;author;Meisler, M. H.;/author;;author;O;apos;Brien, J. E.;/author;;author;Sharkey, L. M.;/author;;/authors;;/contributors;;auth-address;Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-5618, USA. [email protected];/auth-address;;titles;;title;Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects;/title;;secondary-title;J Physiol;/secondary-title;;alt-title;The Journal of physiology;/alt-title;;/titles;;periodical;;full-title;J Physiol;/full-title;;abbr-1;The Journal of physiology;/abbr-1;;/periodical;;alt-periodical;;full-title;J Physiol;/full-title;;abbr-1;The Journal of physiology;/abbr-1;;/alt-periodical;;pages;1841-8;/pages;;volume;588;/volume;;number;Pt 11;/number;;edition;2010/03/31;/edition;;keywords;;keyword;Animals;/keyword;;keyword;Channelopathies/genetics/pathology;/keyword;;keyword;Chromosomes/genetics;/keyword;;keyword;Epilepsy/*genetics</keyword><keyword>Epithelial Sodium Channels/genetics</keyword><keyword>Humans</keyword><keyword>Mutation/physiology</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction</keyword><keyword>Sodium Channels/*genetics</keyword></keywords><dates><year>2010</year><pub-dates><date>Jun 1</date></pub-dates></dates><isbn>0022-3751</isbn><accession-num>20351042</accession-num><urls><related-urls><url>https://deepblue.lib.umich.edu/bitstream/handle/2027.42/79388/jphysiol.2010.188482.pdf?sequence=1</url></related-urls></urls><custom2>PMC2901972</custom2><electronic-resource-num>10.1113/jphysiol.2010.188482</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>10. SCN1A gene is mainly found in ?-aminobutyric acid neurons (GABAergic) and could be colocalized with SCN8A in spinal cord neurons ADDIN EN.CITE <EndNote><Cite><Author>Oliva</Author><Year>2012</Year><RecNum>16</RecNum><DisplayText>11</DisplayText><record><rec-number>16</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936641″>16</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Oliva, M.</author><author>Berkovic, S. F.</author><author>Petrou, S.</author></authors></contributors><auth-address>Florey Neuroscience Institutes, University of Melbourne, Melbourne, Victoria, Australia.</auth-address><titles><title>Sodium channels and the neurobiology of epilepsy</title><secondary-title>Epilepsia</secondary-title><alt-title>Epilepsia</alt-title></titles><periodical><full-title>Epilepsia</full-title><abbr-1>Epilepsia</abbr-1></periodical><alt-periodical><full-title>Epilepsia</full-title><abbr-1>Epilepsia</abbr-1></alt-periodical><pages>1849-59</pages><volume>53</volume><number>11</number><edition>2012/08/22</edition><keywords><keyword>Animals</keyword><keyword>Epilepsy/*genetics/*metabolism/physiopathology</keyword><keyword>Humans</keyword><keyword>Mutation/physiology</keyword><keyword>Voltage-Gated Sodium Channels/chemistry/*physiology</keyword></keywords><dates><year>2012</year><pub-dates><date>Nov</date></pub-dates></dates><isbn>0013-9580</isbn><accession-num>22905747</accession-num><urls><related-urls><url>https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1528-1167.2012.03631.x</url></related-urls></urls><electronic-resource-num>10.1111/j.1528-1167.2012.03631.x</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>11. SCN1A is most commonly associated with Dravet syndromePEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CZXJnaHVpczwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+
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ADDIN EN.CITE.DATA 4.
Some other genes were related to one of the subcategories of epilepsy which was PTE. The genes were IL-1?, GAD1, and A1AR ADDIN EN.CITE <EndNote><Cite><Author>Cotter</Author><Year>2017</Year><RecNum>20</RecNum><DisplayText>1</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936713″>20</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Cotter, D.</author><author>Kelso, A.</author><author>Neligan, A.</author></authors></contributors><auth-address>Queen Mary, University of London, London, UK; Centre for Mind and Brain, University of California Davis, Davis, CA, USA. Queen Mary, University of London, London, UK; Royal London Hospital, London, UK. Queen Mary, University of London, London, UK; Homerton University Hospital, London, UK. Electronic address: [email protected]</auth-address><titles><title>Genetic biomarkers of posttraumatic epilepsy: A systematic review</title><secondary-title>Seizure</secondary-title><alt-title>Seizure</alt-title></titles><periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></periodical><alt-periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></alt-periodical><pages>53-58</pages><volume>46</volume><edition>2017/03/01</edition><keywords><keyword>Epilepsy, Post-Traumatic/*genetics</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Genetic biomarkers</keyword><keyword>Posttraumatic epilepsy</keyword><keyword>Traumatic brain injury</keyword></keywords><dates><year>2017</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1059-1311</isbn><accession-num>28242442</accession-num><urls><related-urls><url>https://www.seizure-journal.com/article/S1059-1311(17)30097-3/pdf</url></related-urls></urls><electronic-resource-num>10.1016/j.seizure.2017.02.002</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>1. The IL-1B gene encodes for the Interleukin-1? which is a proinflammatory cytokine ADDIN EN.CITE <EndNote><Cite><Author>Cotter</Author><Year>2017</Year><RecNum>20</RecNum><DisplayText>1</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936713″>20</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Cotter, D.</author><author>Kelso, A.</author><author>Neligan, A.</author></authors></contributors><auth-address>Queen Mary, University of London, London, UK; Centre for Mind and Brain, University of California Davis, Davis, CA, USA. Queen Mary, University of London, London, UK; Royal London Hospital, London, UK. Queen Mary, University of London, London, UK; Homerton University Hospital, London, UK. Electronic address: [email protected]</auth-address><titles><title>Genetic biomarkers of posttraumatic epilepsy: A systematic review</title><secondary-title>Seizure</secondary-title><alt-title>Seizure</alt-title></titles><periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></periodical><alt-periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></alt-periodical><pages>53-58</pages><volume>46</volume><edition>2017/03/01</edition><keywords><keyword>Epilepsy, Post-Traumatic/*genetics</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Genetic biomarkers</keyword><keyword>Posttraumatic epilepsy</keyword><keyword>Traumatic brain injury</keyword></keywords><dates><year>2017</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1059-1311</isbn><accession-num>28242442</accession-num><urls><related-urls><url>https://www.seizure-journal.com/article/S1059-1311(17)30097-3/pdf</url></related-urls></urls><electronic-resource-num>10.1016/j.seizure.2017.02.002</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>1. It is released in the central nervous system by the activation of microglia and astrocytes and released in the periphery by the macrophages in response to injury in the brain ADDIN EN.CITE <EndNote><Cite><Author>Cotter</Author><Year>2017</Year><RecNum>20</RecNum><DisplayText>1</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936713″>20</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Cotter, D.</author><author>Kelso, A.</author><author>Neligan, A.</author></authors></contributors><auth-address>Queen Mary, University of London, London, UK; Centre for Mind and Brain, University of California Davis, Davis, CA, USA. Queen Mary, University of London, London, UK; Royal London Hospital, London, UK. Queen Mary, University of London, London, UK; Homerton University Hospital, London, UK. Electronic address: [email protected]</auth-address><titles><title>Genetic biomarkers of posttraumatic epilepsy: A systematic review</title><secondary-title>Seizure</secondary-title><alt-title>Seizure</alt-title></titles><periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></periodical><alt-periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></alt-periodical><pages>53-58</pages><volume>46</volume><edition>2017/03/01</edition><keywords><keyword>Epilepsy, Post-Traumatic/*genetics</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Genetic biomarkers</keyword><keyword>Posttraumatic epilepsy</keyword><keyword>Traumatic brain injury</keyword></keywords><dates><year>2017</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1059-1311</isbn><accession-num>28242442</accession-num><urls><related-urls><url>https://www.seizure-journal.com/article/S1059-1311(17)30097-3/pdf</url></related-urls></urls><electronic-resource-num>10.1016/j.seizure.2017.02.002</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>1. GAD1 gene encodes for glutamic acid decarboxylase. There is a suspected link between GAD1 and PTE because there is a link between the involvement of GABAergic neurotransmission in traumatic brain injury (TBI) and seizure susceptibility ADDIN EN.CITE <EndNote><Cite><Author>Cotter</Author><Year>2017</Year><RecNum>20</RecNum><DisplayText>1</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936713″>20</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Cotter, D.</author><author>Kelso, A.</author><author>Neligan, A.</author></authors></contributors><auth-address>Queen Mary, University of London, London, UK; Centre for Mind and Brain, University of California Davis, Davis, CA, USA. Queen Mary, University of London, London, UK; Royal London Hospital, London, UK. Queen Mary, University of London, London, UK; Homerton University Hospital, London, UK. Electronic address: [email protected]</auth-address><titles><title>Genetic biomarkers of posttraumatic epilepsy: A systematic review</title><secondary-title>Seizure</secondary-title><alt-title>Seizure</alt-title></titles><periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></periodical><alt-periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></alt-periodical><pages>53-58</pages><volume>46</volume><edition>2017/03/01</edition><keywords><keyword>Epilepsy, Post-Traumatic/*genetics</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Genetic biomarkers</keyword><keyword>Posttraumatic epilepsy</keyword><keyword>Traumatic brain injury</keyword></keywords><dates><year>2017</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1059-1311</isbn><accession-num>28242442</accession-num><urls><related-urls><url>https://www.seizure-journal.com/article/S1059-1311(17)30097-3/pdf</url></related-urls></urls><electronic-resource-num>10.1016/j.seizure.2017.02.002</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>1. The A1AR gene encodes for the adenosine A1 receptor. It is suspected to be involved in PTE due to how vital adenosine is in the pathology of seizures and TBI ADDIN EN.CITE <EndNote><Cite><Author>Cotter</Author><Year>2017</Year><RecNum>20</RecNum><DisplayText>1</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936713″>20</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Cotter, D.</author><author>Kelso, A.</author><author>Neligan, A.</author></authors></contributors><auth-address>Queen Mary, University of London, London, UK; Centre for Mind and Brain, University of California Davis, Davis, CA, USA. Queen Mary, University of London, London, UK; Royal London Hospital, London, UK. Queen Mary, University of London, London, UK; Homerton University Hospital, London, UK. Electronic address: [email protected]</auth-address><titles><title>Genetic biomarkers of posttraumatic epilepsy: A systematic review</title><secondary-title>Seizure</secondary-title><alt-title>Seizure</alt-title></titles><periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></periodical><alt-periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></alt-periodical><pages>53-58</pages><volume>46</volume><edition>2017/03/01</edition><keywords><keyword>Epilepsy, Post-Traumatic/*genetics</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Genetic biomarkers</keyword><keyword>Posttraumatic epilepsy</keyword><keyword>Traumatic brain injury</keyword></keywords><dates><year>2017</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1059-1311</isbn><accession-num>28242442</accession-num><urls><related-urls><url>https://www.seizure-journal.com/article/S1059-1311(17)30097-3/pdf</url></related-urls></urls><electronic-resource-num>10.1016/j.seizure.2017.02.002</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>1. Adenosine acts as a neuroprotective agent during TBI, but complications in adenosine have been associated with posttraumatic seizures (PTS) ADDIN EN.CITE <EndNote><Cite><Author>Cotter</Author><Year>2017</Year><RecNum>20</RecNum><DisplayText>1</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936713″>20</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Cotter, D.</author><author>Kelso, A.</author><author>Neligan, A.</author></authors></contributors><auth-address>Queen Mary, University of London, London, UK; Centre for Mind and Brain, University of California Davis, Davis, CA, USA. Queen Mary, University of London, London, UK; Royal London Hospital, London, UK. Queen Mary, University of London, London, UK; Homerton University Hospital, London, UK. Electronic address: [email protected]</auth-address><titles><title>Genetic biomarkers of posttraumatic epilepsy: A systematic review</title><secondary-title>Seizure</secondary-title><alt-title>Seizure</alt-title></titles><periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></periodical><alt-periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></alt-periodical><pages>53-58</pages><volume>46</volume><edition>2017/03/01</edition><keywords><keyword>Epilepsy, Post-Traumatic/*genetics</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Genetic biomarkers</keyword><keyword>Posttraumatic epilepsy</keyword><keyword>Traumatic brain injury</keyword></keywords><dates><year>2017</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1059-1311</isbn><accession-num>28242442</accession-num><urls><related-urls><url>https://www.seizure-journal.com/article/S1059-1311(17)30097-3/pdf</url></related-urls></urls><electronic-resource-num>10.1016/j.seizure.2017.02.002</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>1. It is important to distinguish that PTS is not necessarily epileptogenic, but PTE is ADDIN EN.CITE <EndNote><Cite><Author>Cotter</Author><Year>2017</Year><RecNum>20</RecNum><DisplayText>1</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936713″>20</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Cotter, D.</author><author>Kelso, A.</author><author>Neligan, A.</author></authors></contributors><auth-address>Queen Mary, University of London, London, UK; Centre for Mind and Brain, University of California Davis, Davis, CA, USA. Queen Mary, University of London, London, UK; Royal London Hospital, London, UK. Queen Mary, University of London, London, UK; Homerton University Hospital, London, UK. Electronic address: [email protected]</auth-address><titles><title>Genetic biomarkers of posttraumatic epilepsy: A systematic review</title><secondary-title>Seizure</secondary-title><alt-title>Seizure</alt-title></titles><periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></periodical><alt-periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></alt-periodical><pages>53-58</pages><volume>46</volume><edition>2017/03/01</edition><keywords><keyword>Epilepsy, Post-Traumatic/*genetics</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Genetic biomarkers</keyword><keyword>Posttraumatic epilepsy</keyword><keyword>Traumatic brain injury</keyword></keywords><dates><year>2017</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1059-1311</isbn><accession-num>28242442</accession-num><urls><related-urls><url>https://www.seizure-journal.com/article/S1059-1311(17)30097-3/pdf</url></related-urls></urls><electronic-resource-num>10.1016/j.seizure.2017.02.002</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>1.

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Certain mutations/variants can cause different individual responses to anti-epileptic drugs and susceptibility to epilepsy in US Hispanics (primary focus) and other populations. These mutations/variants should increase a person’s susceptibility to epilepsy and should cause the lower effectiveness of individual responses to anti-epileptic drugs. An issue that needs to be addressed is that there is a lack of study on genes affecting US Hispanics in anti-epileptic drug responses and susceptibility to epilepsy.

Materials and methods:
In this review, several genome-wide associations and the candidate genes were cited. The primary reason for this paper was to investigate the genetic variants on anti-epileptic drugs treatment outcomes (or pharmacoresistance) and the association between the genetic variants in epilepsy over the US Hispanic and other populations. I searched up articles on PubMed with the keywords “single nucleotide polymorphism” and “epilepsy” with the filters for humans and English language. There was a total of 108 articles and chose four articles (most recent and relevant). I assessed the full-text of 4 of these reviews and identified five genes (SCN1A, SCN8A, IL-1?, GAD1, and A1AR) that were related to the susceptibility and pharmacogenetics of epilepsy. Further PubMed searches were conducted with the following combinations of keywords “epilepsy,” each gene of the five identified genes, “population,” “anti-epileptic drugs,” and “pharmacogenetics.” I assessed 14 original studies and three meta-analyses from these focused searches. The genes were kept the same, and 16 variants were identified for each of the genes that were related to pharmacogenetics and susceptibility to epilepsy. Ensembl was used to find more variants for SCN8A. I searched for human species and typed “SCN8A” and limited it to infantile epileptic encephalopathy. 8 variants were identified: rs202151337, rs397514738, rs587777721, rs587777722, rs587777723, rs672601319, rs876657399, and rs863223345. dbSNP was used to find the minor allele frequency of each of the 24 identified variants, PharmGKB was used to find the treatment associated with the 24 identified variants, and UCSC Genome Browser was used to find whether each of the identified 24 variants is functionally important (Table 1). The overview of the methods is shown in (Figure 1).

Current findings & results:
Most of the variants/mutations showed increased susceptibility to epilepsy, and some of these variants did affect the pharmacogenetics in epilepsy. The three disease-causing variants associated with SCN1A gene, rs121917965, rs760543, and rs13397210 increased the susceptibility epilepsy, specifically infantile spasms and childhood-onset epilepsyPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5Gcnk8L0F1dGhvcj48WWVhcj4yMDE2PC9ZZWFyPjxSZWNO
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ADDIN EN.CITE.DATA 6, 19. There is one more variant that is both disease-causing and a pharmacogenetic variant associated with SCN1A gene which is rs3812718 and is both linked with increased susceptibility to epilepsy (especially in a Caucasian population) and modifies the effect on the anti-epileptic drug, carbamazepinePEVuZE5vdGU+PENpdGU+PFllYXI+MjAxNDwvWWVhcj48UmVjTnVtPjIyPC9SZWNOdW0+PERpc3Bs
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ADDIN EN.CITE.DATA 2, 16, 20, 21. There are nine disease-causing variants associated with SCN8A gene, rs202151337, rs397514738, rs587777721, rs587777722, rs587777723, rs672601319, rs876657399, rs863223345, and rs201458257 that are linked to increase susceptibility in epilepsy, specifically infantile epileptic encephalopathyPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5CZXJnaHVpczwvQXV0aG9yPjxZZWFyPjIwMTU8L1llYXI+
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ADDIN EN.CITE.DATA 7. There is one disease-causing variant, rs1143634, associated with IL-1B gene that is related to PTE, a subcategory of epilepsy, susceptibility ADDIN EN.CITE <EndNote><Cite><Author>Cotter</Author><Year>2017</Year><RecNum>20</RecNum><DisplayText>1</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936713″>20</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Cotter, D.</author><author>Kelso, A.</author><author>Neligan, A.</author></authors></contributors><auth-address>Queen Mary, University of London, London, UK; Centre for Mind and Brain, University of California Davis, Davis, CA, USA. Queen Mary, University of London, London, UK; Royal London Hospital, London, UK. Queen Mary, University of London, London, UK; Homerton University Hospital, London, UK. Electronic address: [email protected]</auth-address><titles><title>Genetic biomarkers of posttraumatic epilepsy: A systematic review</title><secondary-title>Seizure</secondary-title><alt-title>Seizure</alt-title></titles><periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></periodical><alt-periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></alt-periodical><pages>53-58</pages><volume>46</volume><edition>2017/03/01</edition><keywords><keyword>Epilepsy, Post-Traumatic/*genetics</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Genetic biomarkers</keyword><keyword>Posttraumatic epilepsy</keyword><keyword>Traumatic brain injury</keyword></keywords><dates><year>2017</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1059-1311</isbn><accession-num>28242442</accession-num><urls><related-urls><url>https://www.seizure-journal.com/article/S1059-1311(17)30097-3/pdf</url></related-urls></urls><electronic-resource-num>10.1016/j.seizure.2017.02.002</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>1. There is three disease-causing variants related with GAD1 gene, rs3828275, rs3791878, and rs769391 are linked to PTS ADDIN EN.CITE <EndNote><Cite><Author>Cotter</Author><Year>2017</Year><RecNum>20</RecNum><DisplayText>1</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936713″>20</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Cotter, D.</author><author>Kelso, A.</author><author>Neligan, A.</author></authors></contributors><auth-address>Queen Mary, University of London, London, UK; Centre for Mind and Brain, University of California Davis, Davis, CA, USA. Queen Mary, University of London, London, UK; Royal London Hospital, London, UK. Queen Mary, University of London, London, UK; Homerton University Hospital, London, UK. Electronic address: [email protected]</auth-address><titles><title>Genetic biomarkers of posttraumatic epilepsy: A systematic review</title><secondary-title>Seizure</secondary-title><alt-title>Seizure</alt-title></titles><periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></periodical><alt-periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></alt-periodical><pages>53-58</pages><volume>46</volume><edition>2017/03/01</edition><keywords><keyword>Epilepsy, Post-Traumatic/*genetics</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Genetic biomarkers</keyword><keyword>Posttraumatic epilepsy</keyword><keyword>Traumatic brain injury</keyword></keywords><dates><year>2017</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1059-1311</isbn><accession-num>28242442</accession-num><urls><related-urls><url>https://www.seizure-journal.com/article/S1059-1311(17)30097-3/pdf</url></related-urls></urls><electronic-resource-num>10.1016/j.seizure.2017.02.002</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>1. There are two disease-causing variants associated with A1AR gene, rs3766553, and rs10920573 are related to PTE ADDIN EN.CITE <EndNote><Cite><Author>Cotter</Author><Year>2017</Year><RecNum>20</RecNum><DisplayText>1</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936713″>20</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Cotter, D.</author><author>Kelso, A.</author><author>Neligan, A.</author></authors></contributors><auth-address>Queen Mary, University of London, London, UK; Centre for Mind and Brain, University of California Davis, Davis, CA, USA. Queen Mary, University of London, London, UK; Royal London Hospital, London, UK. Queen Mary, University of London, London, UK; Homerton University Hospital, London, UK. Electronic address: [email protected]</auth-address><titles><title>Genetic biomarkers of posttraumatic epilepsy: A systematic review</title><secondary-title>Seizure</secondary-title><alt-title>Seizure</alt-title></titles><periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></periodical><alt-periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></alt-periodical><pages>53-58</pages><volume>46</volume><edition>2017/03/01</edition><keywords><keyword>Epilepsy, Post-Traumatic/*genetics</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Genetic biomarkers</keyword><keyword>Posttraumatic epilepsy</keyword><keyword>Traumatic brain injury</keyword></keywords><dates><year>2017</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1059-1311</isbn><accession-num>28242442</accession-num><urls><related-urls><url>https://www.seizure-journal.com/article/S1059-1311(17)30097-3/pdf</url></related-urls></urls><electronic-resource-num>10.1016/j.seizure.2017.02.002</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>1. The first variant is associated with PTS and the second variant is associated with PTE ADDIN EN.CITE <EndNote><Cite><Author>Cotter</Author><Year>2017</Year><RecNum>20</RecNum><DisplayText>1</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936713″>20</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Cotter, D.</author><author>Kelso, A.</author><author>Neligan, A.</author></authors></contributors><auth-address>Queen Mary, University of London, London, UK; Centre for Mind and Brain, University of California Davis, Davis, CA, USA. Queen Mary, University of London, London, UK; Royal London Hospital, London, UK. Queen Mary, University of London, London, UK; Homerton University Hospital, London, UK. Electronic address: [email protected]</auth-address><titles><title>Genetic biomarkers of posttraumatic epilepsy: A systematic review</title><secondary-title>Seizure</secondary-title><alt-title>Seizure</alt-title></titles><periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></periodical><alt-periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></alt-periodical><pages>53-58</pages><volume>46</volume><edition>2017/03/01</edition><keywords><keyword>Epilepsy, Post-Traumatic/*genetics</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Genetic biomarkers</keyword><keyword>Posttraumatic epilepsy</keyword><keyword>Traumatic brain injury</keyword></keywords><dates><year>2017</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1059-1311</isbn><accession-num>28242442</accession-num><urls><related-urls><url>https://www.seizure-journal.com/article/S1059-1311(17)30097-3/pdf</url></related-urls></urls><electronic-resource-num>10.1016/j.seizure.2017.02.002</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>1.

Gene Polymorphism Population-Frequency Treatment Response and Drug Functionally important
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ADDIN EN.CITE.DATA 22, 23. (rs3812718)
In a mixed population (Asian and White), patients with epilepsy and CC genotype could have a decreased response to oxcarbazepine or carbamazepine compared to the TT or CT genotype. TT genotype has an increased response compared to CT or CC genotypes. The response can be influenced by clinical and genetic factorsPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5EYWNpPC9BdXRob3I+PFllYXI+MjAxNTwvWWVhcj48UmVj
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rs760543 A-0.429, C-0.315, H-N/A, AS-0.12 rs13397210 A-0.147, C-0.22, H-N/A, AS-0.39 rs3812718 A-0.34, C-0.46, H-0.32, AS-0.404 rs6732655 A-0.152, C-0.308, H-N/A, AS-0.109 rs6730344 A-0.104, C-0.22, H-N/A, AS-0.21 rs10167228 A-0.152, C-0.308, H-N/A, AS-0.109 rs1962842 A-0.152, C-0.308, H-N/A, AS-0.109 rs2298771 A-0.154, C-0.308, H-N/A, AS-0.11 SCN8A rs201458257 A-N/A, C-N/A, H-N/A, AS-N/A N/A rs202151337 A-N/A, C-N/A, H-N/A, AS-N/A rs397514738 A-N/A, C-N/A, H-N/A, AS-N/A rs587777721 A-N/A, C-N/A, H-N/A, AS-N/A rs587777722 A-N/A, C-N/A, H-N/A, AS-N/A rs587777723 A-N/A, C-N/A, H-N/A, AS-N/A rs672601319 A-N/A, C-N/A, H-N/A, AS-N/A rs876657399 A-N/A, C-N/A, H-N/A, AS-N/A rs863223345 A-N/A, C-N/A, H-N/A, AS-N/A IL-1? rs1143634 A-0.123, C-0.25, H-0.174, AS-0.023 N/A GAD1 rs3828275 A-0.172, C-0.447, H-0.35, AS-0.207 N/A rs3791878 A-0.023, C-0.327, H-0.245, AS-0.221 rs769391 A-0.262, C-0.293, H-0.35, AS-0.296 A1AR rs3766553 A-0.377, C-0.465, H-0.47, AS-0.243 N/A rs10920573 A-0.225, C-0.38, H-0.49, AS-0.396 -2857559690A: African, C: Caucasian and/or European, H: Hispanic, AS: Asian, N/A: Not Available
Table 1: Genetic variations of five genes involved in treatment responses in various populations
00A: African, C: Caucasian and/or European, H: Hispanic, AS: Asian, N/A: Not Available
Table 1: Genetic variations of five genes involved in treatment responses in various populations

Discussion, conclusion, and future direction:
SCN1A is the most common mutations in epilepsy and was discovered in the 2000s ADDIN EN.CITE <EndNote><Cite><Author>Meisler</Author><Year>2010</Year><RecNum>19</RecNum><DisplayText>10</DisplayText><record><rec-number>19</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936696″>19</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Meisler, M. H.</author><author>O&apos;Brien, J. E.</author><author>Sharkey, L. M.</author></authors></contributors><auth-address>Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-5618, USA. [email protected]</auth-address><titles><title>Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects</title><secondary-title>J Physiol</secondary-title><alt-title>The Journal of physiology</alt-title></titles><periodical><full-title>J Physiol</full-title><abbr-1>The Journal of physiology</abbr-1></periodical><alt-periodical><full-title>J Physiol</full-title><abbr-1>The Journal of physiology</abbr-1></alt-periodical><pages>1841-8</pages><volume>588</volume><number>Pt 11</number><edition>2010/03/31</edition><keywords><keyword>Animals</keyword><keyword>Channelopathies/genetics/pathology</keyword><keyword>Chromosomes/genetics</keyword><keyword>Epilepsy/*genetics</keyword><keyword>Epithelial Sodium Channels/genetics</keyword><keyword>Humans</keyword><keyword>Mutation/physiology</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction</keyword><keyword>Sodium Channels/*genetics</keyword></keywords><dates><year>2010</year><pub-dates><date>Jun 1</date></pub-dates></dates><isbn>0022-3751</isbn><accession-num>20351042</accession-num><urls><related-urls><url>https://deepblue.lib.umich.edu/bitstream/handle/2027.42/79388/jphysiol.2010.188482.pdf?sequence=1</url></related-urls></urls><custom2>PMC2901972</custom2><electronic-resource-num>10.1113/jphysiol.2010.188482</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>10. Some progress has made in the investigations of SCN1A which led to the identification of several disease-causing variants and pharmacogenetic variants related to Epilepsy. The variant, rs3812718, has been linked to modifying the carbamazepine response in Europeans by conducting changes in GABAergic interneurons excitabilityPEVuZE5vdGU+PENpdGU+PEF1dGhvcj5NZW56bGVyPC9BdXRob3I+PFllYXI+MjAxNDwvWWVhcj48
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ADDIN EN.CITE.DATA 6. Some validations are needed to confirm that some of these disease-causing variants do indeed increase the susceptibilities of epilepsy.

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ADDIN EN.CITE.DATA 8. There have been some suspicions that SCN8A could play a more prominent role than SCN1A in the progression and risk of epilepsy ADDIN EN.CITE <EndNote><Cite><Author>Meisler</Author><Year>2010</Year><RecNum>19</RecNum><DisplayText>10</DisplayText><record><rec-number>19</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936696″>19</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Meisler, M. H.</author><author>O&apos;Brien, J. E.</author><author>Sharkey, L. M.</author></authors></contributors><auth-address>Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-5618, USA. [email protected]</auth-address><titles><title>Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects</title><secondary-title>J Physiol</secondary-title><alt-title>The Journal of physiology</alt-title></titles><periodical><full-title>J Physiol</full-title><abbr-1>The Journal of physiology</abbr-1></periodical><alt-periodical><full-title>J Physiol</full-title><abbr-1>The Journal of physiology</abbr-1></alt-periodical><pages>1841-8</pages><volume>588</volume><number>Pt 11</number><edition>2010/03/31</edition><keywords><keyword>Animals</keyword><keyword>Channelopathies/genetics/pathology</keyword><keyword>Chromosomes/genetics</keyword><keyword>Epilepsy/*genetics</keyword><keyword>Epithelial Sodium Channels/genetics</keyword><keyword>Humans</keyword><keyword>Mutation/physiology</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction</keyword><keyword>Sodium Channels/*genetics</keyword></keywords><dates><year>2010</year><pub-dates><date>Jun 1</date></pub-dates></dates><isbn>0022-3751</isbn><accession-num>20351042</accession-num><urls><related-urls><url>https://deepblue.lib.umich.edu/bitstream/handle/2027.42/79388/jphysiol.2010.188482.pdf?sequence=1</url></related-urls></urls><custom2>PMC2901972</custom2><electronic-resource-num>10.1113/jphysiol.2010.188482</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>10. New methods and techniques in genome sequencing regarding with seizure disorders like epilepsy will replace the older screening techniques soon and allow for identifying more variants ADDIN EN.CITE <EndNote><Cite><Author>Meisler</Author><Year>2010</Year><RecNum>19</RecNum><DisplayText>10</DisplayText><record><rec-number>19</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936696″>19</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Meisler, M. H.</author><author>O&apos;Brien, J. E.</author><author>Sharkey, L. M.</author></authors></contributors><auth-address>Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-5618, USA. [email protected]</auth-address><titles><title>Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects</title><secondary-title>J Physiol</secondary-title><alt-title>The Journal of physiology</alt-title></titles><periodical><full-title>J Physiol</full-title><abbr-1>The Journal of physiology</abbr-1></periodical><alt-periodical><full-title>J Physiol</full-title><abbr-1>The Journal of physiology</abbr-1></alt-periodical><pages>1841-8</pages><volume>588</volume><number>Pt 11</number><edition>2010/03/31</edition><keywords><keyword>Animals</keyword><keyword>Channelopathies/genetics/pathology</keyword><keyword>Chromosomes/genetics</keyword><keyword>Epilepsy/*genetics</keyword><keyword>Epithelial Sodium Channels/genetics</keyword><keyword>Humans</keyword><keyword>Mutation/physiology</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction</keyword><keyword>Sodium Channels/*genetics</keyword></keywords><dates><year>2010</year><pub-dates><date>Jun 1</date></pub-dates></dates><isbn>0022-3751</isbn><accession-num>20351042</accession-num><urls><related-urls><url>https://deepblue.lib.umich.edu/bitstream/handle/2027.42/79388/jphysiol.2010.188482.pdf?sequence=1</url></related-urls></urls><custom2>PMC2901972</custom2><electronic-resource-num>10.1113/jphysiol.2010.188482</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>10. Neuronal cells studies are being considered to aid further the understanding of SCN8A gene dealing with the neuronal sodium channel. However, some limitations with this could be the lack of neuron classes and “circuit-level effects” assessment ADDIN EN.CITE <EndNote><Cite><Author>Meisler</Author><Year>2010</Year><RecNum>19</RecNum><DisplayText>10</DisplayText><record><rec-number>19</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936696″>19</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Meisler, M. H.</author><author>O&apos;Brien, J. E.</author><author>Sharkey, L. M.</author></authors></contributors><auth-address>Department of Human Genetics, University of Michigan, Ann Arbor, MI 48109-5618, USA. [email protected]</auth-address><titles><title>Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects</title><secondary-title>J Physiol</secondary-title><alt-title>The Journal of physiology</alt-title></titles><periodical><full-title>J Physiol</full-title><abbr-1>The Journal of physiology</abbr-1></periodical><alt-periodical><full-title>J Physiol</full-title><abbr-1>The Journal of physiology</abbr-1></alt-periodical><pages>1841-8</pages><volume>588</volume><number>Pt 11</number><edition>2010/03/31</edition><keywords><keyword>Animals</keyword><keyword>Channelopathies/genetics/pathology</keyword><keyword>Chromosomes/genetics</keyword><keyword>Epilepsy/*genetics</keyword><keyword>Epithelial Sodium Channels/genetics</keyword><keyword>Humans</keyword><keyword>Mutation/physiology</keyword><keyword>Reverse Transcriptase Polymerase Chain Reaction</keyword><keyword>Sodium Channels/*genetics</keyword></keywords><dates><year>2010</year><pub-dates><date>Jun 1</date></pub-dates></dates><isbn>0022-3751</isbn><accession-num>20351042</accession-num><urls><related-urls><url>https://deepblue.lib.umich.edu/bitstream/handle/2027.42/79388/jphysiol.2010.188482.pdf?sequence=1</url></related-urls></urls><custom2>PMC2901972</custom2><electronic-resource-num>10.1113/jphysiol.2010.188482</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>10. 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ADDIN EN.CITE.DATA 4. More studies are needed to validate the results of these variants mainly because this is a recently discovered gene linked to epilepsy, and more studies are required to observe how these variants interact with current anti-epileptic drugs in different populations.

The study related with PTE have identified variants associated with the IL-1?, GAD1, and A1AR genes. PTE associated variants and genes were recently detected (2017). Therefore, they have been understudied ADDIN EN.CITE <EndNote><Cite><Author>Cotter</Author><Year>2017</Year><RecNum>20</RecNum><DisplayText>1</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936713″>20</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Cotter, D.</author><author>Kelso, A.</author><author>Neligan, A.</author></authors></contributors><auth-address>Queen Mary, University of London, London, UK; Centre for Mind and Brain, University of California Davis, Davis, CA, USA. Queen Mary, University of London, London, UK; Royal London Hospital, London, UK. Queen Mary, University of London, London, UK; Homerton University Hospital, London, UK. Electronic address: [email protected]</auth-address><titles><title>Genetic biomarkers of posttraumatic epilepsy: A systematic review</title><secondary-title>Seizure</secondary-title><alt-title>Seizure</alt-title></titles><periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></periodical><alt-periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></alt-periodical><pages>53-58</pages><volume>46</volume><edition>2017/03/01</edition><keywords><keyword>Epilepsy, Post-Traumatic/*genetics</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Genetic biomarkers</keyword><keyword>Posttraumatic epilepsy</keyword><keyword>Traumatic brain injury</keyword></keywords><dates><year>2017</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1059-1311</isbn><accession-num>28242442</accession-num><urls><related-urls><url>https://www.seizure-journal.com/article/S1059-1311(17)30097-3/pdf</url></related-urls></urls><electronic-resource-num>10.1016/j.seizure.2017.02.002</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>1. More validations are needed to confirm that these variants do indeed increase the susceptibility of PTE through the use of larger sample size ADDIN EN.CITE <EndNote><Cite><Author>Cotter</Author><Year>2017</Year><RecNum>20</RecNum><DisplayText>1</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936713″>20</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Cotter, D.</author><author>Kelso, A.</author><author>Neligan, A.</author></authors></contributors><auth-address>Queen Mary, University of London, London, UK; Centre for Mind and Brain, University of California Davis, Davis, CA, USA. Queen Mary, University of London, London, UK; Royal London Hospital, London, UK. Queen Mary, University of London, London, UK; Homerton University Hospital, London, UK. Electronic address: [email protected]</auth-address><titles><title>Genetic biomarkers of posttraumatic epilepsy: A systematic review</title><secondary-title>Seizure</secondary-title><alt-title>Seizure</alt-title></titles><periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></periodical><alt-periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></alt-periodical><pages>53-58</pages><volume>46</volume><edition>2017/03/01</edition><keywords><keyword>Epilepsy, Post-Traumatic/*genetics</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Genetic biomarkers</keyword><keyword>Posttraumatic epilepsy</keyword><keyword>Traumatic brain injury</keyword></keywords><dates><year>2017</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1059-1311</isbn><accession-num>28242442</accession-num><urls><related-urls><url>https://www.seizure-journal.com/article/S1059-1311(17)30097-3/pdf</url></related-urls></urls><electronic-resource-num>10.1016/j.seizure.2017.02.002</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>1. Studies on variants associated with PTE should be of great urgency due to the social and economic burden that could be produced by PTE and TBI ADDIN EN.CITE <EndNote><Cite><Author>Cotter</Author><Year>2017</Year><RecNum>20</RecNum><DisplayText>1</DisplayText><record><rec-number>20</rec-number><foreign-keys><key app=”EN” db-id=”zx9w9f52stprx4es0sbpd0zrdv0pt2ftpese” timestamp=”1524936713″>20</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Cotter, D.</author><author>Kelso, A.</author><author>Neligan, A.</author></authors></contributors><auth-address>Queen Mary, University of London, London, UK; Centre for Mind and Brain, University of California Davis, Davis, CA, USA. Queen Mary, University of London, London, UK; Royal London Hospital, London, UK. Queen Mary, University of London, London, UK; Homerton University Hospital, London, UK. Electronic address: [email protected]</auth-address><titles><title>Genetic biomarkers of posttraumatic epilepsy: A systematic review</title><secondary-title>Seizure</secondary-title><alt-title>Seizure</alt-title></titles><periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></periodical><alt-periodical><full-title>Seizure</full-title><abbr-1>Seizure</abbr-1></alt-periodical><pages>53-58</pages><volume>46</volume><edition>2017/03/01</edition><keywords><keyword>Epilepsy, Post-Traumatic/*genetics</keyword><keyword>Genetic Markers</keyword><keyword>Humans</keyword><keyword>Genetic biomarkers</keyword><keyword>Posttraumatic epilepsy</keyword><keyword>Traumatic brain injury</keyword></keywords><dates><year>2017</year><pub-dates><date>Mar</date></pub-dates></dates><isbn>1059-1311</isbn><accession-num>28242442</accession-num><urls><related-urls><url>https://www.seizure-journal.com/article/S1059-1311(17)30097-3/pdf</url></related-urls></urls><electronic-resource-num>10.1016/j.seizure.2017.02.002</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>1.

Most of the SCN1A, IL-1?, GAD1, and A1AR variants were lacking minor allelic frequencies for Hispanics, and there were about two variants for SCN1A that had treatment options. Minor allelic frequencies were lacking for SCN8A due to lack of information in the database and no current treatment options were available for SCN8A, IL-1?, GAD1, and A1AR variants. Primary focus on the Hispanic studies regarding pharmacogenetics and susceptibility to epilepsy are needed due to the lack of information regarding this specific population.

Supplementary Materials Page 1
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