title: Association between the gamma-aminobutyric acid type B receptor 1 and 2 gene polymorphisms and mesial temporal lobe epilepsy in a Han Chinese population.
abstract: An abnormal gamma-aminobutyric acid B receptor composed of gamma-aminobutyric acid type B receptor 1 (GABBR1) and gamma-aminobutyric acid type B receptor 2 (GABBR2) can provoke seizures. This study was designed to assess the contribution of GABBR1 and GABBR2 in mesial temporal lobe epilepsy (MTLE). Two tag single-nucleotide polymorphisms (SNPs) of GABBR1 and four tag SNPs of GABBR2 were selected and genotyped in 318 MTLE patients and 315 non-epileptic individuals. The rs967932 A-allele of GABBR2 increased the risk of MTLE in an additive and a dominant genetic model, respectively (P=0.018, OR=1.305, 95% CI 1.048-1.624 and P=0.003, OR=1.667, 95% CI 1.186-2.343, respectively). rs1999501 and rs944688 of GABBR2, and rs29259 of GABBR1 were thought to be associated with MTLE; however, after a Bonferroni correction, these associations were not observed and only the rs967932 A-allele was found to increase the risk of MTLE in the dominant model (P=0.036). The frequency at which the haplotype G-C-A-C (rs3780428-rs1999501-rs967932-rs944688) occurred in MTLE patients was significantly higher compared to the controls (12.26% vs. 6.51%, P=0.0004) and patients carrying this haplotype exhibited an earlier onset of MTLE (P=0.028). No evidence of significant allelic, genotypic, or haplotypic associations were identified in the tag SNPs of the GABBR1 gene in patients with MTLE, and the polymorphism at G1465A was not observed in our samples. Our results provide the first evidence that common genetic variations in the GABBR2 gene contribute to the risk of MTLE. Moreover, the present results do not support the hypothesis that common variants of GABBR1 contribute substantially to the epileptogenic effect during MTLE in the Han Chinese.
authors.affiliation: National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences; School of Basic Medicine, Peking Union Medical College, Beijing, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Sun
authors.forename: Xilin
authors.initials: X
authors.lastname: Zhu
authors.forename: Liping
authors.initials: L
authors.lastname: Li
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Wu
authors.forename: Hua
authors.initials: H
authors.lastname: Lin
authors.forename: Shuying
authors.initials: S
authors.lastname: Zhu
authors.forename: Aihua
authors.initials: A
authors.lastname: Liu
authors.forename: Te
authors.initials: T
authors.lastname: Du
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Nifang
authors.initials: N
authors.lastname: Niu
authors.forename: Yuping
authors.initials: Y
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000208:ethnology; D002648:Child; D004252:DNA Mutational Analysis / Q000379:methods; D004833:Epilepsy, Temporal Lobe / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B / Q000235:genetics*; D055815:Young Adult
chemical_list: C106350:GABRR2 protein, human; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B