A 5-HT2C receptor promoter polymorphism (HTR2C-759C/T) is associated with obesity in women, and with resistance to weight loss in heterozygotes
A 5-HT2C receptor promoter polymorphism (HTR2C-759C/T) is associated with obesity in women, and with resistance to weight loss in heterozygotes
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DOI：
10.1002/ajmg.b.20143
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发表时间：
2004-04-01
影响因子：
2.8
通讯作者：
Harrison, PJ
中科院分区：
文献类型：
--
作者：
Pooley, EC;Fairburn, CG;Harrison, PJ
血清素5-HT 2C受体（HTR 2C）有助于调节食欲和体重。HTR 2C启动子多态性（-759C/T）与肥胖和抗精神病药物（精神安定药）引起的体重增加有关。我们在120名肥胖妇女（BMI大于或等于30）和104名非肥胖妇女（BMI小于或等于25）中研究了这种多态性。C等位基因在肥胖组中更常见（OR=1.72 [95%CI，1.13-2.64]，P=0.008）。95名肥胖妇女参加了一项关于心理治疗减肥的随机试验。在这些妇女中，杂合子在试验期间比纯合子体重减轻更少（6.8对9.7 kg; P=0.047），6个月后（90.1对83.6 kg; P=0.006）和12个月后（91.8对84.6 kg; P=0.009）体重增加。杂合子也有较高的甘油三酯水平比纯合子。肥胖试验中的C/C受试者在体重减轻或甘油三酯方面与T/T受试者没有差异。在对43名受试者进行的单独RT-PCR研究中，我们发现额叶皮质中HTR 2C mRNA丰度不受-759C/T状态的影响。我们的数据进一步证明HTR 2C启动子变异可能是肥胖的一个危险因素，并且可能通过杂种优势影响肥胖女性的体重减轻。HTR 2C启动子变体的药物遗传学测试在评估直接或间接作用于受体的抗肥胖药物时可能是有价值的。(C)2003 Wiley-Liss，Inc.
The serotonin 5-HT2C 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 (BMIgreater than or equal to30) and 104 non-obese (BMIless than or equal to25) 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. (C) 2003 Wiley-Liss, Inc.