Abstract
Purpose: :
Complement activation has been implicated in the pathogenesis of age related macular degeneration (AMD) and variants in genes encoding complement proteins among them complement factor 3 (C3) were associated with AMD. The rs2231099 single nucleotide polymorphism (SNP) in the gene has recently been associated with increased risk for AMD. We aim to evaluate the association between this SNP and AMD in the Israeli population, its discriminatory accuracy, and its association with phenotype of neovascular AMD (NV-AMD).
Methods: :
DNA was collected from 250 NV-AMD patients and 162 age-matched controls. Genotyping for rs2231099 SNP was performed by a TaqMan assay and was confirmed using sequencing. A receiver operating characteristic (ROC) curve was generated based on genotyping and compared with ROC curves based on genotyping for the Y402H CFH polymorphism and the LOC387715 rs10490924 variant which were previously done for the same population.
Results: :
Heterozygosity for rs2231099 (OR = 1.8, 95% CI = 1.1-2.7, P = 0.01) and the rs2231099 risk allele (OR = 2.2, 95% CI = 1.5-4.2, P = 0.00001) were associated with AMD. There was no association between age of onset of NV-AMD, lesion type according to fluorescein angiography, initial visual acuity, or response to PDT and rs2231099 genotypes. rs2231099 based ROC analysis poorly distinguished between patients and controls [area under the curve (AUC) = 0.6]. By comparison, AUC based on genotyping for the CFH and LOC387715 variants were 0.68 and 0.63, respectively. Logistic regression showed no interaction between the Y402H CFH polymorphism and the C3 variant.
Conclusions: :
The rs2231099 variant in the C3 gene is associated with AMD in the Israeli population. This finding supports the involvement of C3 protein in AMD. Its association is not dependent on the common CFH variant and its discriminatory accuracy for AMD is lower compared with that of CFH and LOC387715.
Keywords: age-related macular degeneration • genetics