强迫症与5-羟色胺转运体基因多态性遗传关联病例对照研究的meta分析

摘要

Objective: To evaluate the association of obsessive-compulsive disorder (OCD) and intron 2 (5-HTTVNTR)and promoter (5-HTTLPR) of SLC6A4 gene polymorphism with meta-analysis and provide evidence for the genetic background of OCD. Methods: We searched for the related case-control designed studies of association between OCD and serotonin transporter gene polymorphisms. The allele and genotype frequencies were extracted from each study, and the pooled odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the allele and genotype of OCD and controls by using software CMA 2. 0. Results: The data from 23 studies were involved in the meta-analysis. The meta-analysis results of association of OCD with the serotonin transporter (5-HTT) gene LPR and VNTR polymorphisms had led to controversial results in different populations. In Asian population, the frequencies of allele L (vs. allele S, OR = 1. 27,95% CI = 1. 05 - 1. 52), genotype LL[ vs. genotype (LS + SS), OR = 1. 78,95% CI = 1. 15 - 2. 74] were higher in OCD patients than those in the controls. In Caucasian population, the frequencies of genotype SS [vs. genotype (LS + SS), OR = 1. 21,95% CI = 1. 02 - 1. 44] were lower. In Caucasian population, the frequencies of genotype 10/10 (vs. genotype10/12 + 12/12, OR =0.41,95% CI = 0. 24 -0. 71) were lower in OCD patients than those in the controls. Conclusion: The findings suggest there be association of OCD and 5-HTT gene polymorphisms. The 5-HTTLPR gene allele L and genotype LL may be risk factors and genotype SS may be protection factor among Asians, while 5-HTTLPR genotype SS may be risk factor and 5-HTTVNTR genotype 10/10 may be protection factor for OCD among Caucasians.%目的:用对病例对照研究的数据作meta分析的方法,综合评价强迫症与5-羟色胺(5-HT)转运体基因的启动子区域(5-HTTLPR)和第二内含子多态性(5-HTTVNTR)的关系,为强迫症的遗传背景提供进一步证据.方法:检索MEDLINE、EMBASE、PubMed、CNKI、万方等数据库,收集强迫症与5-HTTLPR基因多态性及5-HTTVNTR基因多态性相关性的病例对照研究,并以OR值为效应指标,基因型在对照群体中的分布均符合Hardy-Weinberg遗传平衡定律,应用CMA2.0软件对各项数据进行统计分析.结果:符合纳入标准的有23篇文献.结果显示,就强迫症与5 - HTTLPR多态性相关性而言,亚洲人群中,L等位基因较S等位基因(OR=1.27,95％ CI=1.05～1.52)、LL基因型较LS+ SS基因型(OR=1.78,95％ CI=1.15～2.74)在强迫症患者中的分布频率高于对照组；高加索人群中,SS基因型较LS+ LL基因型在强迫症患者中的分布频率高于对照组(OR=1.21,95％ CI 1.02～1.44).就强迫症与5- HTTVNTR多态性相关性而言,高加索人群中10/10基因型较10/12+ 12/12基因型(OR =0.41,95％ CI=0.24～0.71)在强迫症患者中的分布频率低于对照组.结论:现有研究证据提示强迫症与5-HTT基因存在关联,并且在不同种族存在差异.在亚洲人群中5-HTTLPR多态性的L等位基因以及基因型LL可能是强迫症的危险因素,SS基因型是保护因素；在高加索人群中5-HTTLPR多态性的SS基因型则可能是危险因素,5-HTTVNTR基因多态性的10/10基因型是保护因素.