Genotype-phenotype correlation of age-related macular degeneration: influence of complement factor H polymorphism

Background/aims: Complement factor H ( CFH) Y402H polymorphism shows a strong association with age-related macular degeneration (AMD). Although the phenotypic concordance of AMD has been shown in sibling/twin studies, little is known about the genotype phenotype association. In this study, we investigated whether CFH Y402H is associated with early phenotypic features. Methods: Statistical analysis was performed on 420 patients with AMD with complete clinical and genetic data ( graded colour fundus photographs, according to the International Classification and Grading System for AMD and successful testing for CFH Y402H). Results: In this Swiss population, an OR of 2.95 was confirmed for AMD in the presence of at least one risk C allele and OR of 9.05 for the CC homozygotes, corrected for age and sex. No difference was found between the AMD stages. Patients homozygous for the risk allele showed significant association with peripheral drusen ( p= 0.028) and for central drusen location ( p= 0.049). No trend was found for other drusen criteria ( size, total surface, location nasal to disc) and for pigmentary changes. Conclusions: The CFH Y402H polymorphism showed a genotype - phenotype association for some drusen features. Additional genetic factors are likely to influence drusen phenotype.