Contribution of GABRG2 Polymorphisms to Risk of Epilepsy and Febrile Seizure: a Multicenter Cohort Study and Meta-analysis

Batoul Sadat Haerian, Larry Baum, Patrick Kwan, Stacey S. Cherny, Jae Gook Shin, Sung Eun Kim, Bok Ghee Han, Hui Jan Tan, Raymond Azman Ali, Chong Tin Tan, Zahurin Mohamed

Research output: Contribution to journalArticle

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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.

Original languageEnglish
JournalMolecular Neurobiology
DOIs
Publication statusAccepted/In press - 9 Oct 2015

Fingerprint

Febrile Seizures
Multicenter Studies
Meta-Analysis
Epilepsy
Cohort Studies
Hong Kong
Seizures
Neurotransmitter Receptor
GABA Receptors
Linkage Disequilibrium
GABA-A Receptors
Korea
gamma-Aminobutyric Acid
Haplotypes
Genes

Keywords

  • Epilepsy
  • GABRG2
  • Polymorphism
  • Susceptibility

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Contribution of GABRG2 Polymorphisms to Risk of Epilepsy and Febrile Seizure : a Multicenter Cohort Study and Meta-analysis. / Haerian, Batoul Sadat; Baum, Larry; Kwan, Patrick; Cherny, Stacey S.; Shin, Jae Gook; Kim, Sung Eun; Han, Bok Ghee; Tan, Hui Jan; Ali, Raymond Azman; Tan, Chong Tin; Mohamed, Zahurin.

In: Molecular Neurobiology, 09.10.2015.

Research output: Contribution to journalArticle

Haerian, Batoul Sadat ; Baum, Larry ; Kwan, Patrick ; Cherny, Stacey S. ; Shin, Jae Gook ; Kim, Sung Eun ; Han, Bok Ghee ; Tan, Hui Jan ; Ali, Raymond Azman ; Tan, Chong Tin ; Mohamed, Zahurin. / Contribution of GABRG2 Polymorphisms to Risk of Epilepsy and Febrile Seizure : a Multicenter Cohort Study and Meta-analysis. In: Molecular Neurobiology. 2015.
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AU - Kim, Sung Eun

AU - Han, Bok Ghee

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