Association of Combined Complement Factor H Y402H and ARMS/LOC387715 A69S Polymorphisms with Age-related Macular...

Complement factor H (CFH) Y402H (rs1061170) and age-related maculopathy susceptibility2 (ARMS2)/LOC387715 A69S (rs10490924) polymorphisms shown to have significant association with age-related macular degeneration (AMD). In this meta-analysis, we pooled the results of the available association studies between combined ARMS2/LOC387715A69S-CFHY402H genotypes and 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 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 relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), synergy index (S), and multiplicative index (V).

We included eight studies with 2915 AMD patients and 3505 control subjects. Considering the GGTT genotypes as reference lines, the pooled AMD Odds Ratios for stratified combined genotypes were 2.32 (95% CI 1.64-3.28) for GGnon-TT, 2.49 (95% CI 1.72-3.60) for non-GGTT, and 7.82 (95% CI 5.09-12.00) for non-GGnon-TT. Pooled synergy analysis revealed RERI = 4.08 (95% CI 3.15-5.27), AP = 0.50 (95% CI 0.42-0.57), S = 2.31 (95% CI 1.9-2.82), and V = 1.21 (95% CI 0.93-1.49).

This analysis revealed the synergistic and positive multiplicative effect of these two genes indicating that there is a common pathway of ARMS2/LOC387715 and CFH in AMD pathogenesis which may be the complement system pathway.