Joint association of complement component 3 and CC-cytokine ligand2 (CCL2) or complement component 3 and CFH polymorphisms in age-related macular degeneration
Jabbarpoor Bonyadi, MH
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Background: To determine the joint effect of complement component 3(C3 R102G) with CC-cytokine ligand2 (CCL2-2518) or complement factor H (CFH) Y402H polymorphisms on advanced age-related macular degeneration (AMD). Methods: In this case-control study, 233 patients with advanced AMD and 159 unrelated healthy controls enrolled for evaluation. Selected polymorphisms were determined by polymerase chain reaction and restriction fragment length polymorphism. Results: A combination of AA CCL2 (rs1024611) and GG C3 (R102G) genotypes resulted in a super-additivity of the risks: OR = 10.13, 95% CI 1.04â€“98.49, p = 0.04, adjusted OR = 7.74, 95% CI 0.71â€“84.75, p < 0.1, adjusted synergy indices: relative excess risk due to interaction (RERI) = 1.38, the attributable proportion due to interaction (AP) = 24.7% and the synergy index (S) = 1.43. Combination of at-risk genotypes of CFH Y402H and C3 R102G resulted in a strong super-additive risk: adjusted OR = 22.65, 95% CI 2.32â€“220.91, p = 0.007, adjusted AP = 90.4% and the S = 12.86. Attributable proportion of risk owing to C3-CCL2 and C3-CFH interaction calculated at 25% and 90% for advanced AMD. Conclusion: We have previously shown a strong association of C3 (R102G) and CFH Y402H with AMD whereas no association was found for CCL2-2518. This study enclosed strong synergistic association of risk genotypes of C3 and CFH Y402H with AMD. We also revealed synergistic influence of CCL2-2518 and the at-risk genotype of the C3 in AMD with an estimated AP = 50.9% (adjusted AP = 24.7%). Present findings show that CCL2-2518 polymorphism is not an innocent bystander in AMD susceptibility when combined with the at-risk genotype of C3 (R102G). آ© 2017 Taylor & Francis.
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