title: Contribution of GABRG2 Polymorphisms to Risk of Epilepsy and Febrile Seizure: a Multicenter Cohort Study and Meta-analysis.
abstract: Gamma-aminobutyric acid receptor (GABA-A) is the most common receptor of fast synaptic inhibition in the human brain. Gamma protein encoded by the GABRG2 gene is one of the subunits of the GABA-A receptor, which plays an essential role in the function of this receptor. Several studies have identified various febrile seizure (FS) and epilepsy risk variants of GABRG2 gene in different populations, but some others did not support these results. The aim of this case-control study is to investigate whether GABRG2 polymorphisms contribute to susceptibility for FS and epilepsy in pooled data of three cohorts, from Malaysia (composed of Malay, Chinese, and Indian), Hong Kong, and Korea. Furthermore, the pooled dataset of these cohorts with previous reports were meta-analyzed for determining the risk effect size of the rs211037 polymorphism on FS and symptomatic epilepsy (SE). The rs211037, rs210987, rs440218, rs2422106, rs211014, and rs401750 polymorphisms were genotyped in the 6442 subjects (1729 epilepsy and 4713 controls). Results of the case-control study showed associations between rs211037 and the risk of SE in the pooled data from all cohorts (T vs. C, p = 3 × 10(-5), and TT vs. CC, p = 2 × 10(-5)) and the risk of partial seizure in the combined data of Malaysia and Hong Kong (both T vs. C and TT vs. CC, p = 2 × 10(-6)). The rs211037-rs210987 and rs2422106-rs211014-rs401750 haplotypes were also associated with susceptibility to SE in Chinese. Meta-analysis of all Asians identified association between rs211037 and FS and SE (T vs. C, p = 4 × 10(-4), and p = 4 × 10(-3), respectively). In conclusion, rs211037 alone may be a risk factor for FS, partial seizure, and SE, and in linkage disequilibrium with rs210987 can contribute to FS and SE in Asians, particularly in Chinese.
authors.affiliation: Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Lembah Pantai, 59100, Kuala Lumpur, Malaysia. batoolsadat@yahoo.com.
authors.forename: Batoul Sadat
authors.initials: BS
authors.lastname: Haerian
authors.affiliation: School of Pharmacy, The Chinese University of Hong Kong, Shatin, Hong Kong, China. lwbaum@hotmail.com.
authors.forename: Larry
authors.initials: L
authors.lastname: Baum
authors.affiliation: Division of Neurology, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China.
authors.forename: Patrick
authors.initials: P
authors.lastname: Kwan
authors.affiliation: Department of Psychiatry and The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China.
authors.forename: Stacey S
authors.initials: SS
authors.lastname: Cherny
authors.affiliation: Department of Pharmacology and Pharmacogenomics Research Center, College of Medicine, Inje University, Busan, South Korea.
authors.forename: Jae-Gook
authors.initials: JG
authors.lastname: Shin
authors.affiliation: Department of Neurology, Haeundae Paik Hospital, Inje University, Busan, South Korea.
authors.forename: Sung Eun
authors.initials: SE
authors.lastname: Kim
authors.affiliation: Center for Genome Science, Korea National Institute of Health, Chungcheongbuk-do, South Korea.
authors.forename: Bok-Ghee
authors.initials: BG
authors.lastname: Han
authors.affiliation: Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
authors.forename: Hui Jan
authors.initials: HJ
authors.lastname: Tan
authors.affiliation: Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
authors.forename: Azman Ali
authors.initials: AA
authors.lastname: Raymond
authors.affiliation: Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Chong Tin
authors.initials: CT
authors.lastname: Tan
authors.affiliation: Pharmacogenomics Laboratory, Department of Pharmacology, Faculty of Medicine, University of Malaya, Lembah Pantai, 59100, Kuala Lumpur, Malaysia.
authors.forename: Zahurin
authors.initials: Z
authors.lastname: Mohamed
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D003710:Demography; D004827:Epilepsy / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011963:Receptors, GABA-A / Q000235:genetics*; D012307:Risk Factors; D003294:Seizures, Febrile / Q000235:genetics*
chemical_list: C546279:GABRG2 protein, human; D011963:Receptors, GABA-A
keywords: Epilepsy; GABRG2; Polymorphism; Susceptibility