Purpose: To evaluate the association of CC-cytokine ligand 2 CCL2-2518 (rs1024611) single nucleotide polymorphism, complement factor H (CFH Y402H) and their possible interaction in developing advanced age-related macular degeneration (AMD).

Methods: In this case-control study, DNA samples from 266 patients with advanced AMD and 229 healthy controls were genotyped for CCL2 polymorphism and also 254 patients and 164 healthy controls were genotyped for CFH polymorphism. The possible associations of these polymorphisms with susceptibility to AMD independently and in different joint combinations were evaluated.

Results: The genotype frequency for CFH was found to be significantly different between AMD and normal controls (31.5% versus 20.7%, OR = 3.56, p < 0.001 for CC and 52.4% versus 41.5%, OR = 2.96, p < 0.001 for CT genotype). However, no significant association between CCL2 polymorphism and AMD was observed in this cohort (OR = 1.15 and OR = 0.8, p = 0.172). Interestingly, studying the joint effects of two genotypes (TT genotype of CFH Y402H and AG genotype of CCL2-2518) showed more significant protective effect against AMD (p = 0.0001), while the risk effect of CC and CT genotypes of CFH was only visible in the presence of AA genotype of CCL2-2518 (p = 0.044 and p = 0.05).

Conclusion: Complement factor H Y402H polymorphism is strongly associated with advanced type AMD. Although this study revealed no association of CCL2-2518 with AMD, the risk effect of CFH genotypes was only visible in the presence of AA genotype of CCL2-2518. AG genotype of CCL2-2518 in combination with TT genotype of CFH Y402H showed significant protective effect against AMD.