抗精神病药物引发的体重增加与HTR2C基因-759C/T多态性关联的Meta分析

Meta-analysis of the Association between Weight Gain Induced by Antipsychotic Drugs and HTR2C Gene-759C/T Polymorphism

目的探讨抗精神病药物在治疗精神分裂症患者过程中出现的体重增加与5羟色胺2C受体(HTR2C)基因启动子区-759C/T(rs3813929)单核苷酸多态性的关系。方法在Pubmed、Springer、China biology medicine disc(CBM)、谷歌学术、万方数据库等检索1990~2017年精神分裂症患者中有关HTR2C-759C/T基因多态性与抗精神病药物诱导的体重增加关联性研究的文献,对-759C/T位点(CT+TT)/CC,(CT+CC)/TT基因型进行Meta分析。用RevMan version5.3计算OR值及95%可信区间,并按人种因素作亚组分析。结果共有20篇文献符合纳入标准,经Meta分析发现HTR2C-759T与抗精神病药物引发的体重增加呈显著负相关[(CT+TT)/CCOR=0.42,95%CI(0.26~0.66),P=0.0002]。亚组分析中,高加索人群和东亚人群含HTR2C-759T患者的体重增加占比人数显著低于CC基因型患者(高加索人群OR=0.48,95%CI(0.26~0.88),P=0.020,东亚人群OR=0.34,95%CI(0.17~0.69),P=0.002)。HTR2C-759C与抗精神病药物引发的体重增加有正相关趋势[(CT+CC)/TTOR=2.29,95%CI(1.00~5.23),P=0.05]。亚组分析中高加索人群[OR=2.58,95%CI(0.61~10.94),P=0.200]和东亚人群(OR=2.13,95%CI(0.78~5.86),P=0.14)结论一致,差异无统计学意义(P>0.05)。结论HTR2C基因启动子-759C/T单核苷酸多态性与抗精神病药物导致的患者体重增加相关联,携带HTR2C-759T可能是限制体重增加的保护因子。

Objective To investigate the relationship between the weight gain of antipsychotic drugs in the treatment of schizophrenia patients and the single nucleotide polymorphism of the serotonin 2C receptor (HTR2C) gene promoter region-759C/T (rs3813929). Methods Search for HTR2C-759C/T gene polymorphisms associated with antipsychotic-induced weight gain in patients with schizophrenia from 1990 to 2017 in Pubmed, Springer, China biology medicine disc (CBM), Google Scholar, and Wanfang database. For the sex study, a meta-analysis was performed on the -759C/T locus (CT+TT)/CC,(CT+CC)/TT genotype. The OR value and the 95% confidence interval were calculated using RevMan version 5.3 and subgroup analysis was performed by ethnographic factors. Results A total of 20 articles met the inclusion criteria. Meta-analysis found that HTR2C-759T was significantly negatively correlated with weight gain induced by antipsychotic drugs [(CT+TT)/CC OR=0.42, 95%CI(0.26-0.66),P=0.0002]. In the subgroup analysis, the proportion of weight gain in the Caucasian and East Asian populations with HTR2C-759T was significantly lower than that in the CC genotype (Caucasian population OR=0.48,95%CI(0.26-0.88), P=0.020, East Asian population) OR=0.34,95%CI(0.17~0.69),P=0.002). HTR2C-759C had a positive correlation with weight gain induced by antipsychotic drugs [(CT+CC)/TT OR=2.29,95%CI(1.00~5.23),P=0.05].In the subgroup analysis, the Caucasian population [OR=2.58, 95%CI (0.61~10.94), P=0.200] and the East Asian population (OR=2.13,95%CI(0.78~5.86), P=0.14) were consistent,the difference was not statistically significant (P>0.05). Conclusion The HTR2C gene promoter -759C/T single nucleotide polymorphism is associated with weight gain in patients with antipsychotic drugs, and carrying HTR2C-759T may be a protective factor limiting weight gain.