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 [CI] 2.72-15.09, p<0.0001; area under the curve 0.706, CI 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.

Complement factor H and LOC387715 gene polymorphisms in a Greek population with age-related macular degeneration.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of severe visual loss among people over 60 years old. The lack of a broadly effective treatment for AMD underscores the need to identify causative biomarkers that could serve as preventive targets. Thus far, two major susceptibility loci for AMD have been identified, CFH T1277C and LOC387715 G270T. The primary goal of the present study was to elucidate whether these polymorphisms are major genetic determinants of AMD in a Greek population. PATIENTS AND METHODS: A clinic-based, case-control association study was conducted, comprising 100 Greek patients with early and late-stage AMD and 115 independent controls of Caucasian origin. All participants underwent clinical examination including best-corrected visual acuity, intraocular pressure, and dilated fundus examination. Moreover, they were genotyped for CFH T1277C and LOC387715 G270T polymorphisms, by direct sequencing and ARMS PCR, respectively. RESULTS: The frequency of the CFH 1277C allele was significantly higher in AMD patients in comparison with controls while the odds ratios (ORs) for AMD were 4.4-5.5. Statistical comparison of early and advanced AMD patients, on the basis of CFH genotype, revealed that the CFH 1277C allele was associated with both subgroups when compared with the controls (P < 0.001). When statistical comparison was performed between early and advanced patients on the basis of CFH genotypic frequencies, the CC genotype was found to be more prevalent in advanced AMD patients (P = 0.008, OR = 2.3). The frequency of the LOC387715 270 T allele was higher in AMD patients in comparison with controls (P < 0.04) while the ORs for AMD were 1.4-2. No statistically significant differences were located between the early AMD patients and controls, on the basis of LOC387715 genotype (P = 0.189). On the contrary, the T270G polymorphism was associated with advanced AMD (P = 0.04). Moreover, the TT genotype was more prevalent in patients with advanced AMD (P = 0.011, OR = 1.7) when compared with early AMD patients. Assessment of the combined contribution of CFH T1277C and LOC387715 G270T SNPs showed an independent manner of action of these polymorphisms in the development of the disease. CONCLUSIONS: The replication of the reported associations of CFH T1277C polymorphism with AMD suggest that the 1277C 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 in the Greek population.