Background

Complement factor H (CFH) Y402 H (rs1061170) and age-related maculopathy susceptibility2 (ARMS2)/LOC387715 A69 S (rs10490924) polymorphisms shown to have significant association with AMD. In this meta-analysis, we updated and pooled the results of available association studies between combined ARMS2/LOC387715A69 S-CFHY402 H genotypes and AMD to estimate the synergistic effects.

Methods

Heterogeneity of studies was evaluated using Cochran Q-test and I-square index. To modify the heterogeneity in the variables we used random effects model. Meta-analysis was performed using STATA. To estimate the additive or supra-additive effects we calculated RERI (relative excess risk due to interaction), AP (attributable proportion due to interaction), S (synergy index) and V (multiplicative index).

Results

We included 12 studies with 4668 AMD patients and 4936 control subjects. Considering the GGTT genotypes as reference line, the pooled AMD odds ratios for stratified combined genotypes was 2.13 (95% CI 1.64–2.78) for GGnonTT, 2.17 (95% CI 1.63–2.89) for nonGGTT and 7.23 (95% CI 4.95–10.55) for nonGGnonTT. Pooled synergy analysis revealed RERI = 3.90 (95% CI 0.58–10.03), AP = .53 (95% CI 0.09–0.69), S = 2.57 (95% CI 1.27–5.22) and V = 1.47 (95% CI 1.21–1.80).

Conclusion

This updated analysis showed a strong synergistic and positive multiplicative effect of these two genes indicating that there is common pathway of ARMS2/LOC387715 A69 S and CFH Y402 H in AMD pathogenesis which may be complement system pathway.

中文翻译：

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联合补体因子H Y402H和ARMS2 / LOC387715 A69S多态性与年龄相关性黄斑变性的关联：最新的荟萃分析。

背景

补体因子H（CFH）Y402 H（rs1061170）和年龄相关性黄斑病变易感性2（ARMS2）/ LOC387715 A69 S（rs10490924）多态性与AMD有显着关联。在本荟萃分析中，我们更新并汇总了组合的ARMS2 / LOC387715A69 S-CFHY402 H基因型与AMD之间的可用关联研究结果，以评估协同效应。

方法

使用Cochran Q检验和I平方指数评估研究的异质性。为了修改变量的异质性，我们使用了随机效应模型。使用STATA进行荟萃分析。为了估算累加或超累加效果，我们计算了RERI（由于相互作用而引起的相对超额风险），AP（由于相互作用而引起的可占比例），S（协同指数）和V（乘法指数）。

结果

我们纳入了12项针对4668名AMD患者和4936名对照受试者的研究。以GGTT基因型为参考线，对于GGnonTT，分层组合基因型的合并AMD比值比为2.13（95％CI 1.64–2.78），非GGTT为2.17（95％CI 1.63–2.89）和7.23（95％CI 4.95–10.55）。 ）（对于nonGGnonTT）。合并的协同分析显示RERI = 3.90（95％CI 0.58–10.03），AP = .53（95％CI 0.09–0.69），S = 2.57（95％CI 1.27–5.22）和V = 1.47（95％CI 1.21– 1.80）。

结论

这项更新的分析显示这两个基因具有强大的协同增效作用，表明AMD发病机制中存在ARMS2 / LOC387715 A69 S和CFH Y402 H的共同途径，可能是补体系统途径。