Mulder Hans, Franke Barbara, van der-Beek van der Annemarie Aart, Arends Johan, Wilmink Frederik W, Scheffer Hans, Egberts Antoine C G
Division of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
J Clin Psychopharmacol. 2007 Aug;27(4):338-43. doi: 10.1097/JCP.0b013e3180a76dc0.
The use of antipsychotics is associated with metabolic side effects, which put patients with schizophrenia or related disorders at risk for cardiovascular morbidity. The high interindividual variability in antipsychotic-induced metabolic abnormalities suggests that genetic makeup is a possible determinant. In this cross-sectional study, we investigated whether genotypes of the HTR2C receptor are associated with the metabolic syndrome in patients using antipsychotics. Patients were identified from a schizophrenia disease management program. In this program, patients' blood pressure, triglycerides, high-density lipoprotein-cholesterol, and waist circumference are measured regularly during follow-up. The primary end point of our study was the prevalence of the metabolic syndrome as classified by a modified version of the National Cholesterol Education Program's Adult Treatment Panel III. Primary determinants were polymorphisms in the HTR2C receptor gene (HTR2C:c.1-142948[GT]n, rs3813928 [-997 G/A], rs3813929 [-759 C/T], rs518147 [-697 G/C], and rs1414334 [C > G]). The included patients (n = 112) mainly (>80%) used atypical antipsychotics (clozapine, olanzapine, and risperidone). Carriership of the variant alleles of the HTR2C polymorphisms rs518147, rs1414334, and HTR2C:c.1-142948(GT)n was associated with an increased risk of the metabolic syndrome (adjusted odds ratio [OR], 2.62 [95% confidence interval {CI}, 1.00-6.85]; OR, 4.09 [95% CI, 1.41-11.89]; and OR, 3.12 [95% CI, 1.13-8.16]), respectively. Our findings suggest that HTR2C genotypes are associated with antincreased risk of metabolic syndrome in patients taking antipsychotics.
使用抗精神病药物会带来代谢方面的副作用，这使精神分裂症或相关疾病患者面临心血管疾病发病的风险。抗精神病药物诱发的代谢异常存在高度个体差异，这表明基因构成可能是一个决定因素。在这项横断面研究中，我们调查了使用抗精神病药物的患者中，5-羟色胺受体2C（HTR2C）基因的基因型与代谢综合征是否相关。患者来自一个精神分裂症疾病管理项目。在该项目中，患者的血压、甘油三酯、高密度脂蛋白胆固醇和腰围在随访期间会定期测量。我们研究的主要终点是根据美国国家胆固醇教育计划成人治疗小组第三次报告修订版分类的代谢综合征患病率。主要决定因素是HTR2C受体基因的多态性（HTR2C:c.1-142948[GT]n、rs3813928[-997 G/A]、rs3813929[-759 C/T]、rs518147[-697 G/C]和rs1414334[C>G]）。纳入的患者（n = 112）主要（>80%）使用非典型抗精神病药物（氯氮平、奥氮平和利培酮）。HTR2C多态性rs518147、rs1414334和HTR2C:c.1-142948(GT)n的变异等位基因携带者患代谢综合征的风险增加（校正比值比[OR]分别为2.62[95%置信区间{CI}，1.00-6.85]；OR为4.09[95% CI，1.41-11.89]；OR为3.12[95% CI，1.13-8.16]）。我们的研究结果表明，HTR2C基因型与服用抗精神病药物患者代谢综合征风险增加相关。
