Complement C3, C2, and factor B gene polymorphisms and age-related macular degeneration in a Greek cohort study

Purpose: To elucidate whether polymorphisms of C2, C3, and CFB genes are major genetic determinants of age-related macular degeneration (AMD) in a Greek population. Methods: This was a case-control association study comprising 120 Greek patients with early and late-stage AMD and 140 independent controls of Caucasian origin. All participants were genotyped for rs547154, rs2230199, rs641153, and rs12614 polymorphisms by a combination of PCR and direct DNA sequencing assays. Results: The frequency of the rs2230199 G allele (minor allele) was significantly higher in patients with AMD in comparison with controls (0.34 vs 0.22, p = 0.0031) and similar to the frequency of other reported populations. There was a significant difference in the frequencies of the rs2230199 genotypes among cases and controls (p = 0.0055), rs2230199 was found to be a significant predictor of advanced AMD status (odds ratio 6.41, confidence interval [Cl] 2.72-15.09, p<0.0001; area under the curve 0.706, Cl 0.61-0.78, p<0.0001]). For the other single nucleotide polymorphism (SNP) loci, the allele and genotype frequencies did not reach statistical significance. The minor allele frequencies in controls and cases were similar and still much lower than the frequencies reported in other populations. Conclusions: The rs547154, rs641153, and rs12614 SNPs were not associated with AMD development in Greek patients, However, this finding should be viewed with caution as the particular polymorphisms presented with very low frequencies in the Greek population. Finally, the replication of the reported associations of C3 with AMD suggests that the presence of the C3 G allele could serve as a high-risk genetic marker for the development of AMD and the progression of the disease to the advanced clinical stage.