Open Access5‐HT 2A Receptor Gene Promoter Polymorphism in Relation to Abdominal Obesity and Cortisol
Author(s) -
Rosmond Roland,
Bouchard Claude,
Björntorp Per
Publication year - 2002
Publication title -
obesity research
Language(s) - English
Resource type - Journals
eISSN - 1550-8528
pISSN - 1071-7323
DOI - 10.1038/oby.2002.79
Subject(s) - endocrinology , medicine , abdominal obesity , genotype , glucocorticoid receptor , leptin , allele , obesity , insulin , insulin resistance , biology , receptor , gene , waist , genetics
Objective: There is considerable evidence that cortisol secretion is associated with obesity. The regulation of the 5‐hydroxytryptamine receptor 2A ( 5‐HT 2A ) gene might play an essential role because it is involved in the control of cortisol secretion. Therefore, we examined the potential impact of the 5‐HT 2A −1438G/A promoter polymorphism on obesity and estimates of insulin, glucose, and lipid metabolism as well as circulating hormones, including salivary cortisol, in 284 unrelated Swedish men born in 1944. Research Methods and Procedures: The subjects were genotyped by using polymerase chain reaction amplification of the promoter region of the gene for 5‐HT 2A followed by digestion of the reaction product with the restriction enzyme Msp I. Results: The frequencies were 0.39 for allele − 1438A and 0.61 for allele − 1438G . Homozygotes for the − 1438G allele had, in comparison with − 1438A/A subjects, higher body mass index, waist‐to‐hip ratio, and abdominal sagittal diameter. Moreover, cortisol escape from 0.25‐mg dexamethasone suppression was found in subjects with the − 1438A/G genotype. Serum leptin, fasting insulin, and glucose, as well as serum lipids, were not different across the − 1438G/A genotype groups. Discussion: From these results, we suggest the possibility that an abnormal production rate of the 5‐HT 2A gene product might lead to the development of abdominal obesity. The pathophysiology could involve stress factors that destabilize the serotonin‐hypothalamic‐pituitary‐adrenal system in those with genetic vulnerability in the serotonin receptor gene.