5-HTT VNTR多态性与偏头痛关系的系统评价

A systematic review with meta-analysis on the relationship of 5-HTT VNTR and migraine

背景5羟色胺(5-HT)在偏头痛的发病机制中起着重要作用,但是研究5-HT转运体(5-HTT)基因多态性和偏头痛关系的单个遗传关联研究的结果却不一致。目的使用系统评价方法评价5-HTT可变数目串联重复序列(VNTR)多态性和偏头痛的关系。方法广泛检索中英文数据库以发现合格研究,使用随机或固定效应模型计算合并比值比(OR值),使用Q检验评估研究之间异质性,Egger’s(埃格)检验和漏斗图评估发表偏倚。以家族为基础的关联研究则进行描述性分析。结果总共4个研究纳入meta分析,发现在所有人群中,5-HTT VNTR Stin2.12等位基因或12/12基因型增加了偏头痛的发病风险(Stin2.12等位基因:OR:1.34,95%CI:1.09～1.64,P=0.006;12/12基因型:OR:1.55,95%CI:1.17～2.05,P=0.002)。结论现有证据表明,5-HTT VNTR多态性(主要是Stin2.12基因型)增加了偏头痛的发病风险,该结论需大样本研究进一步验证。

Objective Serotonin is known to play an important role in the pathogenesis of migraine,but individual genetic association studies that examine the relationship between polymorphisms of serotonin transporter（5-HTT） gene and migraine have yielded inconsistent results.This study aimed to evaluate the association between 5-HTT VNTR polymorphism and migraine using systematic review with meta-analysis.Methods Relevant studies were identified by searching English and Chinese databases extensively.Allele and genotype frequencies for each included study were extracted.The odds ratio（OR） was calculated using a random-effects or fixed-effects model.Q statistic was used to evaluate homogeneity,and Egger＇s test and Funnel plot were used to assess publication bias.For family-based association studies,a descriptive analysis was carried out;Results A total of 4 studies were identified for meta-analysis.It was found that the 5-HTT VNTR Stin2.12 allele or 12/12 genotype had an increased risk for migraine in the general population（Stin2.12 allele： OR,95% CI：1.34,1.09-1.64,P= 0.006;12/12 genotype： OR,95% CI： 1.55,1.17-2.05,P=0.002）;Conclusion Existing evidence indicates that the 5-HTT VNTR polymorphism（mainly the STin2.12 genotype） is associated with an increased risk of migraine in the general population.Future studies with larger sample sizes will be necessary to confirm the present results.