A 5-HT2C receptor promoter polymorphism (HTR2C - 759C/T) is associated with obesity in women, and with resistance to weight loss in heterozygotes.
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.
Pooley
Edward C
EC
University Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford OX3 7JX, United Kingdom.
Fairburn
Christopher G
CG
Cooper
Zafra
Z
Sodhi
Monsheel S
MS
Cowen
Philip J
PJ
Harrison
Paul J
PJ
D000328:Adult; D001835:Body Weight; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009765:Obesity / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D044405:Receptor, Serotonin, 5-HT2C / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012307:Risk Factors; D014280:Triglycerides / Q000378:metabolism; D015431:Weight Loss / Q000235:genetics*
D012333:RNA, Messenger; D044405:Receptor, Serotonin, 5-HT2C; D014280:Triglycerides