Association of polymorphisms in complement component 3 with age-related macular degeneration in an Iranian population

Background: Age related macular degeneration (AMD) is the leading cause of irreversible blindness in the elderly population. Inflammatory mediators play an important role in AMD pathogenesis and immune-related gene polymorphisms are shown to increase the risk. Complement system is an important mediator of the immunity system and several genes encoding proteins involved in this system are associated with susceptibility to AMD. The central element of the complement cascade, C3 has been a plausible candidate since its cleavage product C3a was found in drusen. This study was planned to evaluate the association of C3-rs2230199 (R102G) variants with advanced type AMD in this cohort. Materials and methods: In this case-control study, 494 participants consisting of 266 AMD patients (187 wet AMD and 79 advanced dry AMD) and 228 samples from unrelated healthy controls were enrolled for evaluation. Extracted-DNA samples were amplified to obtain fragments including the polymorphic region. Results: The distribution of the R102G genotypes was significantly different in the AMD patients compared to controls (p = 0.001). The Odds Ratio compared to CC individuals was 1.69 (95% CI 1.152.49) for GC individuals and 6.48 (95% CI1.87-22.43) for GG individuals. The Odds Ratio compared to the C allele was 2.31 (95% CI 0.48-11) for the G allele. GG and GC genotypes and G allele were significantly associated with both types of advanced-AMD. Individuals carrying GG genotype have over a six-fold risk of developing AMD in comparison to those carrying the CC genotype in this cohort. Our meta-analysis pooled data showed that our homozygous individuals for GG have a higher risk of AMD compared to previous publications in different nations (p = 0.017). Conclusions: Our study shows C3 to be a relatively strong susceptibility gene for advanced-type-AMD (exudative-and-geographic-atrophy) in an Iranian population.