RGD Reference Report - Allelic variants in the GABA(A)alpha6 receptor subunit gene (GABRA6) is associated with abdominal obesity and cortisol secretion. - Rat Genome Database

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Allelic variants in the GABA(A)alpha6 receptor subunit gene (GABRA6) is associated with abdominal obesity and cortisol secretion.

Authors: Rosmond, R  Bouchard, C  Bjorntorp, P 
Citation: Rosmond R, etal., Int J Obes Relat Metab Disord. 2002 Jul;26(7):938-41.
RGD ID: 1626491
Pubmed: PMID:12080446   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.ijo.0802022   (Journal Full-text)

INTRODUCTION: Cortisol is involved in the regulation of adipose-tissue differentiation, function and distribution, and in excess causes abdominal obesity. At the level of the brain, cortisol secretion is partly controlled by gamma-aminobutyric acid (GABA), which is the major inhibitory neurotransmitter in the vertebrate brain, and acts by binding to GABA(A) receptors. METHOD: We examined the potential impact of a 1519T>C polymorphism in the GABA(A)alpha6 receptor subunit (GABRA6) gene on obesity and obesity-related phenotypes as well as circulating hormones, including salivary cortisol in 284 unrelated Swedish men born in 1944. 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. RESULTS: The frequency of allele T was 0.54 and 0.46 for allele C. Carriers for the T allele (n=211) had borderline significantly higher waist-to-hip ratio (P=0.094) and abdominal sagittal diameter (P=0.084) compared to homozygotes for the C allele (n=56). The homozygotes for the T allele had, in comparison to heterozygotes, significantly (P=0.004-0.024) higher mean cortisol levels at 11:45 am, and 30, 45 and 60 min after a standardized lunch and, finally, at 5:00 pm. In addition, T/T subjects had significantly (P=0.031) higher diurnal cortisol secretion compared to T/C subjects. Other hormones, glucose and serum lipids were not different across the genotype groups. CONCLUSION: These findings suggest a role of the 1519T>C polymorphism in GABRA6 in the predisposition to hypercortisolism and perhaps abdominal obesity. The pathophysiology may involve various environmental factors, particularly stress, that destabilize the GABA-hypothalamic-pituitary-adrenal systems in those with genetic vulnerability.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Cushing Syndrome  IAGP 1626491DNA:polymorphism:3' utr:1519T>C and abdominal obesity and hypercortisolismRGD 
obesity  IAGP 1626491DNA:polymorphism:3' utr:1519T>C and abdominal obesity and hypercortisolismRGD 

Objects Annotated

Genes (Rattus norvegicus)
Gabra6  (gamma-aminobutyric acid type A receptor subunit alpha6)


Additional Information