Gregoor Jochem G, van der Weide Jan, Mulder Hans, Cohen Dan, van Megen Harold J G M, Egberts Antoine C G, Heerdink Eibert R
Psychiatric Hospital Meerkanten, Ermelot, the Netherlands.
J Clin Psychopharmacol. 2009 Feb;29(1):21-5. doi: 10.1097/JCP.0b013e31819359be.
Weight gain is one of the most serious adverse effects of atypical antipsychotic agents. Genetic factors influence the risk of an individual to gain weight. The objective of our study was to determine whether the LEPR Q223R polymorphism and the LEP promoter 2548G/A polymorphism are associated with obesity in a group of male and female patients using atypical antipsychotic drugs. A cross-sectional study design was used. The study population consisted of 200 patients aged between 18 and 65 years, diagnosed with a psychotic disorder, all of whom had been using an atypical antipsychotic for at least 3 months. The primary outcome measure was the presence of obesity. Determinants were the LEPR Q223R (rs1137101) polymorphism and the LEP promoter 2548G/A single nucleotide polymorphism ([SNP] rs7799039). Of the 200 included patients, 61 (31%) were obese. In females, the LEPR 223QR (adjusted odds ratio, 0.11; 95% confidence interval [CI], 0.02-0.54) and LEPR 223RR (adjusted odds ratio, 0.07; 95% CI, 0.01-0.63) genotypes were associated with a lower risk of obesity. In males, this association was not found. In females, the average body weight was 13.6 kg more (95% CI, 1.11-26.1) in the LEPR 223QQ group compared with the LEPR 223RR group. No significant association was found between the LEP promoter 2548G/A polymorphism and obesity. Taken together, the results of our study show that the LEPR Q223R polymorphism may be associated with obesity in women with a psychotic disorder treated with atypical antipsychotic drugs and stress the importance of stratification for gender when investigating the role of variations of the LEP- and LEPR genes on the metabolic side effects of antipsychotic medications.
体重增加是非典型抗精神病药物最严重的不良反应之一。遗传因素影响个体体重增加的风险。我们研究的目的是确定在一组使用非典型抗精神病药物的男性和女性患者中，瘦素受体（LEPR）Q223R多态性和瘦素（LEP）启动子2548G/A多态性是否与肥胖相关。本研究采用横断面研究设计。研究人群包括200名年龄在18至65岁之间、被诊断患有精神障碍的患者，所有患者均使用非典型抗精神病药物至少3个月。主要观察指标是肥胖的存在情况。决定因素是LEPR Q223R（rs1137101）多态性和LEP启动子2548G/A单核苷酸多态性（[SNP] rs7799039）。在纳入研究的200名患者中，61名（31%）患有肥胖症。在女性中，LEPR 223QR基因型（调整后的优势比为0.11；95%置信区间[CI]为0.02 - 0.54）和LEPR 223RR基因型（调整后的优势比为0.07；95%CI为0.01 - 0.63）与较低的肥胖风险相关。在男性中未发现这种关联。在女性中，与LEPR 223RR组相比，LEPR 223QQ组的平均体重多13.6千克（95%CI为1.11 - 26.1）。未发现LEP启动子2548G/A多态性与肥胖之间存在显著关联。综上所述，我们的研究结果表明，LEPR Q223R多态性可能与使用非典型抗精神病药物治疗的患有精神障碍的女性肥胖相关，并强调在研究LEP和LEPR基因变异对抗精神病药物代谢副作用的作用时，性别分层的重要性。
