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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

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

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.[1]

References

  1. Allelic variants in the GABA(A)alpha6 receptor subunit gene (GABRA6) is associated with abdominal obesity and cortisol secretion. Rosmond, R., Bouchard, C., Björntorp, P. Int. J. Obes. Relat. Metab. Disord. (2002) [Pubmed]
 
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