Low frequency of the CFH Polymorphism T1277C Contributes to a Low Prevalence of AMD in a Sardinian Genetic Isolate

Purpose: to ascertain the prevalence of age related macular degeneration (AMD) and to examine the role of the T1277C polymorphism (Y402H) of the CFH gene in a Sardinian genetic isolate (Talana). Methods: Eight hundred volunteers from Talana were subjected to a complete ophthmalogical examination during a one year period. We then evaluated those subjects over 50 years old for the clinical signs of AMD. Additionally, patients from a Sardinian ophthmalogical clinic (49 people affected by exudative AMD), and a matched control group were studied. Furthermore, 100 healthy Sardinan blood donors were genotyped. Detailed questionaries were administered to Talana inhabitants to obtain demographic information, smoking history, alcohol intake, sunlight exposure, medical history, medication use and diet. Participants underwent a full ophthalmological and a general medical examination. AMD lesions were assessed on colour fundus photographs using a modification of the Wisconsin Age-related Maculopathy Grading System protocol. Blood samples were taken for biochemical determinations and for genetical analysis for the polymorphism T1277C (Y402H rs1061170), of the CFH gene Results: In Talana, no cases of the exudative form of AMD were found; the observed prevalence of early AMD fundus changes was 5.8% (95% C.I. 1.1-7.6) and the observed prevalence of geographic atrophy was 0.8% ( 95% C.I. 0.1-1.6). In the blood donors, the frequencies were 15% C-C, 40% C-T and 45% T-T genotypes. Moreover, we found a significant difference in the distributions the genotypes in the case-control group, (p = 0.002). Notably, the presence of the C-C genotype increased the risk of AMD (OR 6.6, 95% C.I. [2.170-20.337]). In contrast, the C-C genotype frequency was significantly lower in Talana compared with the blood donors, (5.3% vs 15.0%. p value = 0.003 ). Conclusions: Importantly the T1277C polymorphism seems to denote elevated risk for AMD in the general Sardinian population, as previously reported in other ethnic groups, and hence could serve as a valuable tool for diagnostic and prevention programs. The absence of exudative form of AMD observed in Talana could be related to the low frequency of the Histidine at codon 402, but we can not rule out the role of other factors, i.e. environment, in explaining these clinical findings.