Disease relevance of GABRA6

• Allelic variants in the GABA(A)alpha6 receptor subunit gene (GABRA6) is associated with abdominal obesity and cortisol secretion [1].
• CONCLUSION: These findings suggest a role of the 1519T>C polymorphism in GABRA6 in the predisposition to hypercortisolism and perhaps abdominal obesity [1].

Psychiatry related information on GABRA6

• Our findings support a role for DRD2 (E8) and GABRA6 (Pro385Ser) in perceived parenting [2].
• In the present study, 56 healthy subjects underwent genotyping to determine the influence of the T1521C single nucleotide polymorphism (SNP) in the GABA(A)alpha6 receptor subunit gene (GABRA6) on the hormonal and autonomic responses to psychological stress induced by the Trier Social Stress Test (TSST) [3].
• Polymorphisms on GABRA1 and GABRA6 genes displayed significant associations with mood disorders in female patients [4].

High impact information on GABRA6

• Association of the GABRB2 1412T allele with alcohol dependence was detected in both populations (Finns, P = .01; Southwestern Native Americans, P = .008), and the GABRA6 1519T allele was associated in both Finns (P = .01) and Southwestern Native Americans (P = .03) [5].
• In both populations, the haplotype localization implicates the region containing the Pro385Ser GABRA6 polymorphism and 2 other polymorphisms at GABRA6 [5].
• Chromatin immunoprecipitation also showed that NFI proteins are bound to the GABRA6 promoter in these cells in vivo [6].
• Comparison of transcript levels in schizophrenia patients and unaffected siblings found lower patient expression of GABRA6 and coexpressed genes of GABRA1 [7].
• In the first stage, associations were detected in a Portuguese patient sample with single nucleotide polymorphisms (SNPs) and haplotypes in GABRA1 (P=0.00062-0.048), GABRP (P=0.0024-0.042), and GABRA6 (P=0.0065-0.0088) [7].

Biological context of GABRA6

• Further evidence for clustering of human GABAA receptor subunit genes: localization of the alpha 6-subunit gene (GABRA6) to distal chromosome 5q by linkage analysis [8].
• We report here a microsatellite polymorphism within the human alpha 6-subunit gene (GABRA6) [8].
• A gene cluster consisting of the four gamma-aminobutyric acidA (GABAA) receptor subunit genes GABRA1, GABRA6, GABRAB2, and GABRG2 was assigned to a yeast artificial chromosome (YAC) contig of 5q33 [9].
• Similarly, the Pro385Ser variant of GABRA6, the polymorphic gene for GABA(A) receptor alpha6 subunit, has been associated with alcohol- and depression-related traits; and rat pups maintained a more immature GABAR phenotype after brief separation distress [2].
• An interaction between DRD2 and GABRA6 genotypes on father rejection (P = 0.010) and parents rejection (P = 0.030) was also observed [2].

Associations of GABRA6 with chemical compounds

• Microarray expression analysis showed low level of expression of GABA-A receptor (GABRA6) and glutamate transporter (EAAT4) [10].

Other interactions of GABRA6

• These studies demonstrated that nuclear factor I (NFI) proteins are required for both transgenic GABRA6 promoter activity as well as endogenous expression of this gene in cerebellar granule neurons [6].

Analytical, diagnostic and therapeutic context of GABRA6

• The subjects were genotyped by using PCR amplification of the 3' non-coding region of the GABRA6 gene followed by digestion with the restriction enzyme AlwNI [1].

References