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Low Prevalence of the N363S Polymorphism of the Glucocorticoid Receptor in South Asians Living in the United Kingdom

School of Clinical Medical Sciences (A.A.S., N.C.U., K.G.M.M.A., C.P.F.R., J.U.W.), Northern Institute for Cancer Research (J.A.E.I., A.G.H., C.P.F.R.), and School of Population and Health Sciences (N.C.U., M.W.), University of Newcastle, Newcastle upon Tyne NE2 4HH, United Kingdom; and Public Health Sciences Section (R.S.B.), University of Edinburgh Medical School, Edinburgh EH8 9AG, United Kingdom

Address all correspondence and requests for reprints to: Dr. Christopher P. F. Redfern, Medical Molecular Biology Group, 4th Floor, Cookson Building, University of Newcastle Medical School, Newcastle upon Tyne NE2 4HH, United Kingdom. E-mail: chris.redfern{at}ncl.ac.uk.

Similarities between clinical states of glucocorticoid excess and obesity have raised suspicion of a link between the two conditions. An Asn363Ser (N363S) polymorphism in exon 2 of the glucocorticoid receptor has been associated with glucocorticoid sensitivity and excess adiposity in people of European origin. Compared with Europid populations, South Asians have a higher prevalence of cardiovascular risk factors, including type 2 diabetes and central obesity. The aim of this study was to determine the prevalence of the 363S allele in people of South Asian origin living in northeast England in relation to obesity and other cardiovascular risk factors. DNA from 142 males and 153 females was characterized for 363S allele status. Two N363S heterozygotes were identified; both subjects had raised body mass index and central obesity. Despite a higher prevalence of overweight (body mass index 25 kg/m²) people in the South Asian group compared with the Europid population in the same geographical area (66 vs. 56%, respectively), the 363S allele frequency was significantly lower in the South Asian group (0.3 vs. 3%, respectively). Therefore, the N363S polymorphism is unlikely to be an important factor in obesity and/or dysmetabolic traits in people of South Asian origin living in the United Kingdom.

Abbreviations: BMI, Body mass index; CAD, coronary artery disease; dHPLC, denaturing HPLC; GC, glucocorticoid; NHP, Newcastle Heart Project; WC, waist circumference; WHR, waist to hip ratio.

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