亚甲基四氢叶酸还原酶C677T基因多态性与抑郁症遗传易感性研究的Meta分析

目的系统评价亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase，MTHFR）基因C677T多态性与抑郁症风险的遗传关联性。方法检索、筛选有关MTHFRC677T基因多态性与抑郁症风险的遗传关联性研究文献，通过Meta分析以合并优势比（oddsratio，OR）及其95％置信区间评价关联强度，并用GRADE进行证据质量评级。结果共纳入25篇合格文献，包括4048例抑郁症患者和12827例健康对照组。Meta分析结果提示C677T基因属于共显性遗传模型：T等位基因（Tvs．C：OR。=1．25；z=3．82，P=0．000）和TT基因型（1，rVS．CC：OR，=1．55；z=3．79，P=0．000）均增加抑郁症风险，但CTVS．CC基因型除外（OR，=1．13；z=1．78，P=0．076）。分层分析提示非老年组的关联度高于老年组（60岁为界）。基于Meta回归的亚组分析提示中国亚组（OR0=1．58，z=3．95，P=0．000；ORl=2．55，z=3．92，P=0．000；OR2=1．43，Z=2．72，P=0．007）比非中国亚组（OR0=1．12，Z=2．10，P=0．035；OR1=1．23，z=2．23，P=0．025；OR：=1．06，z=0．74，P=0．456）的风险度更高。GRADE证据评级共得到1个中等质量、3个低质量和7个极低质量证据。结论MTHFRC677T基因多态性与抑郁症存在遗传关联性，但不同人群、不同发病年龄间关联度不同。GRADE证据强度普遍不高。

Meta-analysis of the methylenetetrahydrofolate reductase C677T polymorphism and susceptibility to de- pression

Objective To evaluate the association between methylenetetrahydrofolate reduetase （MTH- FR） C677T gene polymorphism and depression risk.Methods Available studies containing genotype frequencies of MTHFR C677T were chosen,and pooled odds ratio （ OR ） with 95% confidence interval （ CI ） was used to as- sess the strength of the association.Results Twenty-five eligible studies including 4 048 cases and 12 827 controls were identified. Meta-analysis showed a significant effect in the co-dominant model （T vs. C： OR o = 1.25; Z= 3.82, P=0.000;Tl＇vs. CC： OR 1= 1.55, Z=3.79, P=0.000;except CT vs. CC： OR 2= 1.13; Z= 1.78, P= 0.076） .Stratified analysis denoted that there was significantly higher risk in depression onset before 60 years old than depression onset after 60 years old. In subgroup analysis stratified by regressive meta-analysis, MTHFR C677T variant was statistically significantly relevant to depression ri~k in Chinese populations （ OR 0 = 1.58, Z= 3.95, P= 0.000; OR 1 = 2.55, Z= 3.92, P= 0.000; OR 2 = 1.43, Z= 2.72, P= 0.007） , but not in no-Chinese populations （ OR 0 = 1.12, Z= 2.10, P= 0.035 ; OR 1 = 1.23, Z= 2.23, P= 0.025 ; OR 2 = 1.06, Z= 0.74, P= 0.456）. Evidentiary strength rated by GRADE showed that 1 study moderate, 3 studies low and 7 stdudies very low.Conclusion Our study provides evidence for a hereditary association between the MTHFR C677T variant and depression susceptibil- ity, whereas there is an obvious variety in different regions, ethnicities and onset age.