Association of Combined Complement Factor H Y402h and Arms2/Loc387715 A69s Polymorphisms With Age-Related Macular Degeneration: An Updated Meta-Analysis Publisher Pubmed



Jabbarpoor Bonyadi MH¹ ; Yaseri M² ; Soheilian M¹
Source: Ophthalmic Genetics Published:2020

Abstract

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. © 2020, © 2020 Taylor & Francis Group, LLC.