Association of GABRG2 rs211037 polymorphism with susceptibility to epilepsy in Asians: a multicentre cohort study and meta-analysis

Abstract

PURPOSE:The gamma-aminobutyric acid receptor subunit gamma-2 (GABRG2) gene encodes GABR-gamma2 protein, which has been implicated in susceptibility to epilepsy. Several studies have investigated whether the synonymous GABRG2 rs211037 polymorphism is a risk factor for various epilepsy types including febrile seizure (FS), idiopathic generalized epilepsy (IGE) and symptomatic epilepsy (SE), however results have been inconclusive. Therefore, we examined association of this polymorphism in FS, IGE, SE, and cryptogenic epilepsy (CE), through both a multicenter case control study and a meta-analysis. METHODS: The rs211037 was genotyped in Hong Kong Chinese and in Malaysian Chinese, Indian, and Malay participants. Genotypes of 5101 participants, of which 1769 were from Malaysia and 3332 from Hong Kong, were included in this case-control study. KEY FINDINGS:Of the 1179 patients, 66%, 13%, and 21% were Chinese, Indians, and Malays, respectively. Of the Chinese patients, 37% were from Malaysia and 63% were from Hong Kong. Significant association was observed between rs211037 polymorphism and susceptibility to SE (T vs. Cp=0.000003 and TT vs. CC, p=0.00001) or to epilepsy with FS (T vs. C p=0.02 and CT vs. CC, p=0.02) in overall Chinese and to IGE in Chinese from Malaysia (TT vs. CC, p=0.01), but not to CE. Meta-analysis revealed a strong association between rs211037 with FS and SE in Asians for alleles (p=0.02, p=0.002 and p<0.00001, respectively) and for all genotype models. SIGNIFICANCE: Our data suggests that GABRG2 rs211037 polymorphism is a risk factor for susceptibility to SE and FS in Asians, particularly in Chinese.