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.