5-HTR2A基因多态性与抗精神分裂症药物疗效相关性的meta分析

Meta-analysis of the Correlation Between 5-HTR2A Gene Polymorphism and the Efficacy of Anti- schizophrenia Drugs

关键词:  精神分裂症  5-HTR2A  rs6311  rs6313  抗精神分裂症药  meta分析

Key words:  schizophrenia  5-HTR2A  rs6311  rs6313  anti-schizophrenia drugs  meta analysis

摘要:

目的 应用meta分析明确5-羟色胺2A受体(5-HTR2A)基因rs6311(-1438A>G)和rs6313(102T>C)位点多态性与抗精神分裂症药物疗效的相关性。方法 计算机检索PubMed、Embase、ScienceDirect、Web of Science和中国知网、万方、维普、中国生物医学文献数据库，获取近20年有关5-HTR2A基因多态性与抗精神分裂症药物疗效关系的相关文献，提取数据。采用Review Manager 5.3软件进行meta分析。结果 共纳入27篇文献。分别对5-HTR2A基因rs6311、rs6313位点的等位基因和基因型多态性与抗精神分裂症药物治疗有效率、减分率的关联性进行meta分析，并以时间、药物、地区3种因素分别进行亚组分析。rs6311位点有效率数据合并显示，等位基因A>G多态性与抗精神病药疗效无关，而亚组分析显示中国人群中等位基因A患者的有效率更高；减分率数据合并显示AG基因型患者的抗精神病药物减分率高于GG。对于rs6313位点，等位基因T>C多态性与抗精神病药有效率无关，而与基因型多态性存在关联，TC基因型患者的氯丙嗪有效率高于TT基因型患者；减分率数据也显示TC患者的药物减分率比TT患者高，亚组分析显示在中国群体中基因型TC患者减分率高于TT患者，而其他国家群体中CC基因型患者减分率高于TT患者，在利培酮和1999—2009群体中TC基因型患者的减分率均高于CC基因型患者。结论 5-HTR2A基因多态性与抗精神分裂症药物疗效的关联受时间、药物、地区的影响，但总体而言rs6311位点AG基因型、rs6313位点TC基因型是抗精神分裂症药物疗效好的预测因子。

Abstract:

OBJECTIVE To determine the correlation between the polymorphisms of rs6311 (-1438A>G) and rs6313(102T>C) of 5-HTR2A gene and the efficacy of anti-schizophrenia drugs by meta-analysis. METHODS The association of 5-HTR2A gene polymorphisms with the efficacy of anti-schizophrenia drugs were retrieved from PubMed, Embase, ScienceDirect, Web of Science, CNKI, Wanfang, Weipu, and the Chinese Biomedical Literature Database in the past two decades. Review Manager 5.3 was used to meta analysis. RESULTS A total of 27 articles were included. The meta-analysis was performed on the correlation between allele and genotype of rs6311 and rs6313 locus of 5-HTR2A gene and anti-schizophrenia drug treatment effectiveness and reductive ratio, and subgroup analysis was performed by three factors: time, drug, and region. Meta-merge analysis of the effectiveness data of rs6311 locus showed that the allele A>G polymorphism was not associated with the efficacy of anti-schizophrenia drugs, and the subgroup analysis showed that the efficiency of allele A patients in the Chinese population was higher. The reductive ratio data showed that the anti-schizophrenia drugs reductive ratio of AG genotype patients was higher than that of GG. For the rs6313 locus, the allelic T>C polymorphism was not associated with the efficacy of anti-schizophrenia drugs, while the genotype polymorphism was associated. The effectiveness of chlorpromazine treatment in patients with TC genotype was higher than that of TT. The reductive ratio data also showed that the reductive ratio of TC patient was higher than that of TT. Subgroup analysis also showed that the reductive ratio of genotype TC patients in the Chinese population was higher than that of TT. While, the CC genotype patients in other countries had a higher reductive ratio than TT. The reductive ratio of TC genotype patients in the risperidone treatment and 1999—2009 populations were both higher than that of CC. CONCLUSION The association between 5-HTR2A gene polymorphism and the efficacy of anti-schizophrenia drugs is affected by time, drug, and region. But overall, the rs6311 locus AG genotype and the rs6313 locus TC genotype are good predictors of anti-schizophrenia drugs.