Interactions among different genetic loci in age-related macular degeneration

Purpose: To evaluate the possible synergistic effect of at risk genotypes of ARMS2/LOC387715 (A69S), DNA repair SMUG1 rs3087404, CCL2–2518, C3 (R102G), CFH Y402H, complement factor B (L9H), and complement factor I (CFI) (G119R) in advanced age-related macular degeneration compared to those of healthy controls. Elucidation of synergistic effects between different genetic loci may clarify their pathogenetic pathways.

Methods: We calculated relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S) to estimate the additive or supra-additive effects of the mentioned genotypes.

Results: ARMS2-CFH RERI = 4.78 (95% CI 2.17–10.61), AP = 0.65 (95% CI 0.33–0.83), S = 4.11 (95% CI 1.40–12.06)], and CFH-C3 combinations RERI = 2.71 (95% CI 0.04–7.01) AP = 0.47 (95% CI ?0.03–0.7) S = 2.30 (95%CI 0.97–5.45)] have the most significant levels of synergism and C3-CFI combination RERI = ?1.65 (95%CI ?4.34–0.06), AP = ?0.92(95%CI ?3.09 – ?0.09), S = 0.32 (95%CI 0.09 = 1.20)] has the most significant level of antagonism.

Conclusion: Among different genotype combinations ARMS2-CFH and CFH-C3 combinations have the most significant levels of synergism and C3-CFI combination has the most significant level of antagonism in AMD patients.