Department of Psychiatry, Taipei Veterans General Hospital, Division of Psychiatry, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Schizophr Res. 2011 Feb;125(2-3):179-86. doi: 10.1016/j.schres.2010.11.030. Epub 2010 Dec 23.
Previous research indicates that common single-nucleotide polymorphisms (SNPs) in the serotonin 5-HT2C receptor gene (HTR2C) are associated with metabolic syndrome (MetS) related to antipsychotic treatment. This study analyzes a large sample of patients with schizophrenia treated with atypical antipsychotics to determine whether variation in the HTR2C is associated with MetS.
Six tag SNPs, capturing all common genetic variations in the HTR2C gene in the Han population, were genotyped in 456 Chinese schizophrenic inpatients treated with atypical antipsychotics (clozapine: 171, olanzapine: 91, and risperidone: 194).
Single-marker based analysis shows that of the six HTR2C SNPs, the rs498177 SNP showed a significant association with MetS in female patients, and the C allele was associated with an increased risk of MetS (for genotype TT/TC/CC: MetS vs. non-MetS=50%/27%/23% vs. 69%/28%/3%, and for allele T/C: MetS vs. non-MetS=63%/37% vs. 83%/17%, p=0.0007). Haplotype analysis shows that the A-C type of rs521018-rs498177 in the HTR2C gene significantly decreased the risk of MetS (corrected p=0.0108) in female patients.
The results of this study support the role of HTR2C genetic variants in susceptibility to MetS in patients treated with atypical antipsychotics. However, this association is gender-dependent.
先前的研究表明，5-羟色胺 5-HT2C 受体基因（HTR2C）中的常见单核苷酸多态性（SNP）与抗精神病药物治疗相关的代谢综合征（MetS）有关。本研究分析了一大群接受非典型抗精神病药物治疗的精神分裂症患者，以确定 HTR2C 的变异是否与 MetS 相关。
在 456 名接受非典型抗精神病药物（氯氮平：171 名，奥氮平：91 名，利培酮：194 名）治疗的中国精神分裂症住院患者中，对 6 个标签 SNP 进行基因分型，这些 SNP 可捕获汉族人群中 HTR2C 基因的所有常见遗传变异。
基于单标记的分析表明，在 6 个 HTR2C SNP 中，rs498177 SNP 与女性患者的 MetS 显著相关，C 等位基因与 MetS 的风险增加相关（对于基因型 TT/TC/CC：MetS 与非 MetS=50%/27%/23%与 69%/28%/3%，对于等位基因 T/C：MetS 与非 MetS=63%/37%与 83%/17%，p=0.0007）。单体型分析显示，HTR2C 基因中 rs521018-rs498177 的 A-C 型显著降低了女性患者 MetS 的风险（校正后 p=0.0108）。
本研究的结果支持 HTR2C 遗传变异在接受非典型抗精神病药物治疗的患者中对 MetS 易感性的作用。然而，这种关联是性别依赖性的。
