Associations of complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genotypes with subtypes of polypoidal choroidal vasculopathy.

Purpose: To clarify whether complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genotypes are associated with subtypes of polypoidal choroidal vasculopathy (PCV), such as polypoidal choroidal neovascularization (CNV) and typical PCV.

Methods: Two hundred eighty-seven patients were categorized as having polypoidal CNV (85 patients) or typical PCV (202 patients) on the basis of indocyanine green angiographic findings. In total, 277 subjects without age-related macular degeneration (i.e., free of PCV and CNV), served as controls. I62V (rs800292) in the CFH gene and A69S (rs10490924) in the ARMS2 gene were genotyped, and case-control studies were performed in subjects with these PCV subtypes.

Results: The polypoidal CNV group included no subjects homozygous for the A/A genotype of rs800292, whereas 7% of the typical PCV group had this genotype. Case-control studies of polypoidal CNV and typical PCV showed significant differences in all distributions of rs10490924 between these two groups. In contrast, the distributions of rs10490924 did not differ between the typical PCV and control groups. Logistic regression analysis with adjustment for confounding factors showed the distributions of rs10490924 to differ significantly between the controls and polypoidal CNV cases (P = 2.1 × 10(-10); OR, 10.87). The T/T genotype was significantly more common in the polypoidal CNV than in the typical PCV group (P = 3.6 × 10(-14); OR, 19.61).

Conclusions: PCV may be genetically divisible into polypoidal CNV and typical PCV. The rs800292 variant of the CFH gene is a potential marker for typical CNV. The rs10490924 variant of the ARMS2 gene was shown to be associated with polypoidal CNV. Typical PCV was not associated with this variant.