The GABA type A receptor α5 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 alpha 5 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 11 disorder patients, compared with control subjects. The haplotype analysis showed that IVS 1-21G > A/IVS2-26A > T was associated with bipolar I disorder, and the IVS 1-21A/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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.