Jabbarpoor Bonyadi Mohammad Hossein, Yaseri Mehdi, Bonyadi Mortaza, Soheilian Masoud, Nikkhah Homayoun
a Ocular Tissue Engineering Research Center, Ophthalmic Research Center , Shahid Beheshti University of Medical Sciences , Tehran , Iran.
b Department of Biostatistics and Epidemiology , Tehran University of Medical Sciences , Tehran , Iran.
Ophthalmic Genet. 2017 Jul-Aug;38(4):308-313. doi: 10.1080/13816810.2016.1237664. Epub 2017 Jan 17.
The age-related maculopathy susceptibility2 (ARMS2)/LOC387715 A69S (rs10490924) polymorphism and cigarette smoking have been shown to have significant association with AMD. In this meta-analysis we used the results of available association studies of combined ARMS2/LOC387715 genotypes and cigarette smoking with AMD to estimate the possible synergistic or multiplicative effects.
Heterogeneity of studies was evaluated using the Cochran Q-test and the I-square index. To compensate for the heterogeneity of the variables in the study we used a random effects model. Meta-analysis was performed using STATA. To estimate the additive or supra-additive effects, we calculated relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), synergy index (S), and multiplicative index (V).
We could include four studies with 1982 AMD patients and 1797 control subjects. Considering the GG-no smoking as a reference line the meta-analysis result of AMD odds ratios for stratified combined factors was 3.05 (95% CI 2.32-4.02) for nonGG-no smoking, 2.24 (95% CI 1.39-3.63) for GG-smoking and 4.59 (95% CI 3.51-6.01) for nonGG-smoking. The meta-analysis of synergy analysis revealed RERI = 2.01 (95% CI 1.01-3.25), AP = 0.40 (95% CI 0.22-0.54), S = 2.02 (95% CI 1.35-3.01), and V = 1.31 (95% CI 0.94-1.83).
This analysis revealed the synergistic effect of these two factors indicating that there is a common pathway of ARMS2/LOC387715 and smoking in AMD pathogenesis which may be the complement system pathway.
年龄相关性黄斑病变易感性2（ARMS2）/ LOC387715 A69S（rs10490924）基因多态性与吸烟已被证明与年龄相关性黄斑变性（AMD）存在显著关联。在这项荟萃分析中，我们利用ARMS2/ LOC387715基因组合型与吸烟和AMD的现有关联研究结果，来估计可能的协同或相乘效应。
采用Cochran Q检验和I²指数评估研究的异质性。为弥补研究中变量的异质性，我们使用随机效应模型。使用STATA进行荟萃分析。为估计相加或超相加效应，我们计算了交互作用所致相对超额危险度（RERI）、交互作用所致归因比例（AP）、协同指数（S）和相乘指数（V）。
我们纳入了4项研究，共1982例AMD患者和1797例对照。以GG-不吸烟作为参照线，分层组合因素的AMD优势比的荟萃分析结果为：非GG-不吸烟组为3.05（95%CI 2.32 - 4.02），GG-吸烟组为2.24（95%CI 1.39 - 3.63），非GG-吸烟组为4.59（95%CI 3.51 - 6.01）。协同分析的荟萃分析显示，RERI = 2.01（95%CI 1.01 - 3.25），AP = 0.40（95%CI 0.22 - 0.54），S = 2.02（95%CI 1.35 - 3.01），V = 1.31（95%CI 0.94 - 1.83）。
该分析揭示了这两个因素的协同效应，表明在AMD发病机制中ARMS2/ LOC387715与吸烟存在共同途径，可能是补体系统途径。
