A 5-HT2C receptor promoter polymorphism (HTR2C - 759C/T) is associated with obesity in women, and with resistance to weight loss in heterozygotes.

Abstract

The serotonin 5-HT(2C) receptor (HTR2C) helps regulate appetite and body weight. An HTR2C promoter polymorphism (-759C/T) has been associated with obesity and with weight gain in response to antipsychotic (neuroleptic) drugs. We studied this polymorphism in 120 obese women (BMI > or = 30) and 104 non-obese (BMI < or = 25) women. The C allele was commoner in the obese group (OR = 1.72 [95% CI, 1.13-2.64], P = 0.008). Ninety-five of the obese women participated in a randomized trial of psychological treatments for weight loss. Among these women, heterozygotes lost less weight during the trial than did homozygotes (6.8 vs. 9.7 kg; P = 0.047) and weighed more 6 months (90.1 vs. 83.6 kg; P = 0.006) and 12 months (91.8 vs. 84.6 kg; P = 0.009) later. Heterozygotes also had higher triglyceride levels than homozygotes. C/C subjects in the obesity trial did not differ from T/T subjects in terms of weight loss or triglycerides. In a separate RT-PCR study of 43 subjects, we found that HTR2C mRNA abundance in frontal cortex was unaffected by -759C/T status. Our data extend the evidence that HTR2C promoter variation may be a risk factor for obesity and, perhaps through heterosis, influences weight loss by obese women. Pharmacogenetic testing of HTR2C promoter variants may be valuable when evaluating anti-obesity drugs which act directly or indirectly on the receptor.

• Authors: Edward C Pooley, Christopher G Fairburn, Zafra Cooper, Monsheel S Sodhi, Philip J Cowen, Paul J Harrison
• Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (Am J Med Genet B Neuropsychiatr Genet) Vol. 126B Issue 1 Pg. 124-7 (Apr 01 2004) ISSN: 1552-4841 [Print] United States
• PMID: 15048662 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2003 Wiley-Liss, Inc.

Chemical References

• RNA, Messenger
• Receptor, Serotonin, 5-HT2C
• Triglycerides

Topics

• Adult
• Body Weight
• Female
• Heterozygote
• Homozygote
• Humans
• Obesity (genetics)
• Polymorphism, Genetic (genetics)
• Promoter Regions, Genetic (genetics)
• RNA, Messenger (genetics)
• Receptor, Serotonin, 5-HT2C (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• Risk Factors
• Triglycerides (metabolism)
• Weight Loss (genetics)