The GABA type A receptor alpha5 subunit gene is associated with bipolar I disorder.
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.
Otani
Kyohei
K
Department of Neuropsychiatry, Okayama University Graduate School of Medicine and Dentistry, Shikata-cho 2-5-1, Okayama 700-8558, Japan.
Ujike
Hiroshi
H
Tanaka
Yuji
Y
Morita
Yukitaka
Y
Katsu
Takeshi
T
Nomura
Akira
A
Uchida
Naohiko
N
Hamamura
Takashi
T
Fujiwara
Yutaka
Y
Kuroda
Shigetoshi
S
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
C496250:Gabra5 protein, mouse; D011963:Receptors, GABA-A