5-HT2A receptor gene promoter polymorphism in relation to abdominal obesity and cortisol.
OBJECTIVE
There is considerable evidence that cortisol secretion is associated with obesity. The regulation of the 5-hydroxytryptamine receptor 2A (5-HT2A) 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-HT2A -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.


METHODS
The subjects were genotyped by using polymerase chain reaction amplification of the promoter region of the gene for 5-HT2A followed by digestion of the reaction product with the restriction enzyme MspI.


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.


CONCLUSIONS
From these results, we suggest the possibility that an abnormal production rate of the 5-HT2A 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.
Rosmond
Roland
R
Department of Clinical Chemistry, Sahlgrenska University Hospital, Göteborg, Sweden. rolandrosmond@hotmail.com
Bouchard
Claude
C
Björntorp
Per
P
D000005:Abdomen; D000483:Alleles; D001824:Body Constitution; D015992:Body Mass Index; D019003:Deoxyribonuclease HpaII / Q000378:metabolism; D003907:Dexamethasone; D005787:Gene Frequency; D005938:Glucocorticoids; D006720:Homozygote; D006854:Hydrocortisone / Q000032:analysis*; D009765:Obesity / Q000235:genetics* / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011401:Promoter Regions, Genetic / Q000235:genetics*; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000235:genetics*; D012463:Saliva / Q000737:chemistry
D005938:Glucocorticoids; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D003907:Dexamethasone; D019003:Deoxyribonuclease HpaII; D006854:Hydrocortisone