Endocrine Abstracts (2004) 7 P41

The N363S polymorphism of the glucocorticoid receptor in South Asians in the North East

AA Syed1, JAE Irving2, CPF Redfern1,2, AG Hall2, NC Unwin1,3, M White1,3, RS Bhopal4, KGMM Alberti1 & JU Weaver1


1Clinical Medical Sciences, University of Newcastle, UK; 2Northern Institute for Cancer Research, University of Newcastle, UK; 3Population & Health Sciences, University of Newcastle, UK; 4Public Health Sciences Section, University of Edinburgh, UK.


Some people with obesity have hormonal, metabolic and circulatory changes that constitute the metabolic syndrome that resemble characteristics of patients with Cushing's syndrome. A link between the two conditions, possibly genetic, has therefore been suspected, and the glucocorticoid receptor gene (GRL, 5q31-q32) has been one of the candidate genes.

The single nucleotide polymorphism N363S is an ATT to GTT missense alteration within exon 2 of GRL that results in a receptor variant (GR363S) with an asparagine to serine substitution in a modulatory region. Several studies have linked N363S with glucocorticoid-sensitivity, excess adiposity and type 2 diabetes in people of European origin. This group has previously reported an association with central obesity in Europid males in the Newcastle Heart Project (NHP). Compared to Europid populations, South Asians have a higher prevalence of central obesity and type 2 diabetes. The aim of this study was to determine the prevalence of the 363S allele in people of South Asian origin living in north-east England in relation to obesity and other cardiovascular risk factors.

DNA from 142 male and 153 female South Asian subjects from the NHP was characterised for 363S allele status by denaturing high performance liquid chromatography (WAVE Systems, Transgenomic, UK) and/or pyrosequencing (Pyrosequencing AB, Sweden). The local research ethics committee approved the study. Two N363S heterozygotes were identified; both subjects, a male and a female, had raised body mass index (BMI) and central obesity. Despite a higher prevalence of overweight (BMI greater than 25 kg/m2) in the South Asian group compared to the Europid group (66% vs. 56%), the 363S allele frequency was significantly lower (0.3% vs. 3%; p < 0.001). Therefore, the N363S polymorphism is unlikely to be an important factor accounting for obesity and/or the metabolic syndrome in people of South Asian origin living in the United Kingdom.

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