ABSTRACT
Purpose: 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.
Methods: 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).
Results: 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).
Conclusion: 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.
Acknowledgments
The authors would like to express greatest appreciation to all the participants in the study especially to Dr. Zou GY from Department of Epidemiology & Biostatistics, Schulich School of Medicine & Dentistry and Robarts Clinical Trials Inc. Western University, London, Ontario, Canada, for providing necessary information and interaction analysis software.
Funding
This research was funded by the Ophthalmic Research Center (Grant no. 1321).
Declaration of interest
The authors declare no conflict of interest.