title: The GABA type A receptor alpha5 subunit gene is associated with bipolar I disorder.
abstract: Several genetic studies have revealed that bipolar disorders are linked with the chromosomal locus of 15q11-q13, where the gamma-aminobutyric acid (GABA) receptor alpha5 subunit gene (GABRA5) locates. GABA is one of the major neurotransmitters that may be involved in the pathogenesis of bipolar disorder. Five polymorphisms in the GABRA5 gene, -754C>T in the promoter region, IVS1-21G>A, IVS2-26T>A, (*)302C>T in 3'-UTR of exon 5, and a CA repeat polymorphism in the 3' flanking region were examined in a Japanese population. IVS1-21G>A exhibited significant differences in the distribution of the genotype and allele frequency in bipolar I disorder patients but not in bipolar II disorder patients, compared with control subjects. The haplotype analysis showed that IVS1-21G>A/IVS2-26A>T was associated with bipolar I disorder, and the IVS1-21A/IVS2-26T haplotype was a negative risk factor for susceptibility to the disorders (odds ratio: 0.57, 95% confidence interval: 0.44-0.73). These results suggest that the GABRA5 gene may confer susceptibility to bipolar I disorder.
authors.affiliation: Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, Shikata-cho 2-5-1, Okayama 700-8558, Japan.
authors.forename: Kyohei
authors.initials: K
authors.lastname: Otani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ujike
authors.forename: Yuji
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yukitaka
authors.initials: Y
authors.lastname: Morita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Katsu
authors.forename: Akira
authors.initials: A
authors.lastname: Nomura
authors.forename: Naohiko
authors.initials: N
authors.lastname: Uchida
authors.forename: Takashi
authors.initials: T
authors.lastname: Hamamura
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Shigetoshi
authors.initials: S
authors.lastname: Kuroda
mesh_terms: D001714:Bipolar Disorder / Q000453:epidemiology* / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011963:Receptors, GABA-A / Q000235:genetics*; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D016037:Single-Blind Method
chemical_list: C496250:Gabra5 protein, mouse; D011963:Receptors, GABA-A