Effects of Cataract Surgery and Polymorphisms in CFH and ARMS2 on the risk of Age-related Macular Degeneration

Abstract

Purpose: To determine the independent and joint effects of cataract surgery and genetic polymorphism in the CFH and ARMS2 genes on the risk of early age-related macular degeneration (AMD)

Methods: A total of 9,529 eyes of 4,918 participants from the Singapore Malay Eye Study and the Singapore Indian Eye Study were analyzed. Participants underwent a structured questionnaire and a detailed ocular examination, including slit lamp examinations for lens status and dilated fundus photography. AMD grading was done based on the retinal photos according to the Wisconsin age-related maculopathy grading system. Previous cataract surgery was defined as pseudophakia or aphakia. Genotyping was performed using Illumina Human 610 BeadChip platform. SNP rs10801555 (Y402H) in the CFH gene and rs3750847 in ARMS2 were included for analysis.

Results: We found a weak association between previous cataract surgery and early AMD (odds ratio [OR]=1.36; 95% confidence interval [CI]: 0.99-1.87). In individuals without previous cataract surgery, the risk of early AMD was similar between those with the CFH Y402H wild-type genotype (GG) and the Y402H risk genotypes (genotype GA: OR = 0.95 [95% CI: 0.72-1.24]; AA: OR = 0.90 [95% CI 0.52-1.55]). In contrast, individuals with both previous cataract surgery and the Y402H risk genotype were more likely to have early AMD, with an OR of 1.63 [95% CI: 1.11-2.41] for the GA genotype and an OR of 2.46 (95% CI: 1.26-4.80) for the AA genotype, compared to those with the GG genotype and without cataract surgery. The interaction between previous cataract surgery and CFH Y402H on the risk of early AMD remained significant (P = 0.045) after adjusting for age, gender, genetic ancestry, smoking status, diabetes mellitus, hypertension, hyperlipidemia and chronic kidney disease. There was no significant interaction between cataract surgery and the ARMS2 rs3750847.

Conclusions: A trend towards an association between cataract surgery and early AMD was found. There is significant gene-environment interaction between CFH genetic polymorphism and cataract surgery on the risk of early AMD, suggesting a role of the complement system in the pathogenesis of AMD following cataract surgery.

Keywords: 412 age-related macular degeneration • 445 cataract • 539 genetics