BACKGROUND: The gamma-aminobutyric acid (GABA) neurotransmitter system has been implicated in the pathogenesis of mood disorders. The GABRA1 gene encodes one of the subunits of GABA-A receptor and is located on human chromosome 5q34-q35, which is a region reportedly linked to mood disorders. We examined the GABRA1 gene as a candidate for mood disorders. METHODS: We performed mutation screening of GABRA1 in 24 Japanese bipolar patients and evaluated associations in Japanese case-control subjects consisting of 125 patients with bipolar disorder, 147 patients with depressive disorders, and 191 healthy control subjects. Associations were confirmed in the National Institute of Mental Health (NIMH) Initiative Bipolar Pedigrees, which consists of 88 multiplex pedigrees with 480 informative persons. RESULTS: We identified 13 polymorphisms in the GABRA1 gene. Nonsynonymous mutations were not found. Association of a specific haplotype with affective disorders was suggested in the Japanese case-control population (corrected p=.0008). This haplotype association was confirmed in the NIMH pedigrees (p=.007). CONCLUSIONS: These results indicate that the GABRA1 gene may play a role in the etiology of bipolar disorders.
BACKGROUND: The gamma-aminobutyric acid (GABA) neurotransmitter system has been implicated in the pathogenesis of mood disorders. The GABRA1 gene encodes one of the subunits of GABA-A receptor and is located on human chromosome 5q34-q35, which is a region reportedly linked to mood disorders. We examined the GABRA1 gene as a candidate for mood disorders. METHODS: We performed mutation screening of GABRA1 in 24 Japanese bipolarpatients and evaluated associations in Japanese case-control subjects consisting of 125 patients with bipolar disorder, 147 patients with depressive disorders, and 191 healthy control subjects. Associations were confirmed in the National Institute of Mental Health (NIMH) Initiative Bipolar Pedigrees, which consists of 88 multiplex pedigrees with 480 informative persons. RESULTS: We identified 13 polymorphisms in the GABRA1 gene. Nonsynonymous mutations were not found. Association of a specific haplotype with affective disorders was suggested in the Japanese case-control population (corrected p=.0008). This haplotype association was confirmed in the NIMH pedigrees (p=.007). CONCLUSIONS: These results indicate that the GABRA1 gene may play a role in the etiology of bipolar disorders.
Authors: Karine Audouze; Agnieszka Sierakowska Juncker; Francisco J S S A Roque; Konrad Krysiak-Baltyn; Nils Weinhold; Olivier Taboureau; Thomas Skøt Jensen; Søren Brunak Journal: PLoS Comput Biol Date: 2010-05-20 Impact factor: 4.475
Authors: Berit Kerner; Anna J Jasinska; Joseph DeYoung; Maricel Almonte; Oi-Wa Choi; Nelson B Freimer Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2009-01-05 Impact factor: 3.568
Authors: H Le-Niculescu; N J Case; L Hulvershorn; S D Patel; D Bowker; J Gupta; R Bell; H J Edenberg; M T Tsuang; R Kuczenski; M A Geyer; Z A Rodd; A B Niculescu Journal: Transl Psychiatry Date: 2011-04-26 Impact factor: 6.222
Authors: Bikash K Mishra; Tianxia Wu; Inna Belfer; Colin A Hodgkinson; Leonardo G Cohen; Carly Kiselycznyk; Albert Kingman; Robert B Keller; Qiaoping Yuan; David Goldman; Steven J Atlas; Mitchell B Max Journal: Mol Pain Date: 2007-07-26 Impact factor: 3.395