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Aims  To determine the differential effects of genetic polymorphism in  CFH  and  ARMS2  on risk of age-related macular degeneration (AMD) between phakic vs. pseudophakic/aphakic eyes.    Methods  9,529 eyes of 4,918 participants from the Singapore Malay Eye Study and Singapore Indian Eye Study were analyzed. Participants had detailed eye examinations, including slit-lamp examinations and dilated fundus photography. AMD grading was performed according to the Wisconsin age-related maculopathy grading system. Lens status was defined. Single nucleotide polymorphisms (SNPs) rs10801555 (Y402H) within  CFH  and rs3750847 in  ARMS2  were assessed. The main outcome measure was early AMD or any AMD.    Results  No significant associations between the  CFH  Y402H genotypes and early AMD were found in phakic individuals. In contrast, among pseudophakic/aphakic individuals, the  CFH  Y402H risk genotypes were significantly associated with higher odds of early AMD, with an OR of 1.57 (95% CI: 1.07–2.29) for GA genotype and 2.40 (95% CI: 1.25–4.61) for AA genotype, compared to those with GG genotype. There was significant interaction between pseudophakic/aphakic status and  CFH  Y402H variant on risk of early AMD (p = 0.037), adjusting for age, gender, and the first 5 genetic principal components. No significant interaction was found between lens status and  ARMS2  rs3750847.    Conclusions    CFH  genetic polymorphism and pseudophakic/aphakic status may have a potential synergistic effect on early AMD, suggesting roles for the complement system and related pathways in the pathogenesis of AMD in eyes after cataract surgery.

plos one

Lens Status Influences the Association between CFH Polymorphisms and Age-Related Macular Degeneration: Findings from Two Population-Based Studies in Singapore