CFH and ARMS2 variations in age-related macular degeneration, polypoidal choroidal vasculopathy, and retinal...

To seek an association in Japanese individuals between the CFH polymorphisms Y402H and I62V and the ARMS2 polymorphism A69S and age-related macular degeneration (AMD) or its three subtypes: typical (t)AMD, polypoidal choroidal vasculopathy (PCV), and retinal angiomatous proliferation (RAP).

The three polymorphisms were genotyped in a case-control study of 1351 control subjects and 962 patients with AMD.

The three polymorphisms correlated with AMD (Y402H, P = 1.54 × 10(-6); I62V, P =1.94 × 10(-29); and A69S, P = 9.56 × 10(-43)). The I62V and A69S polymorphisms were associated with all three subtypes: tAMD (P = 3.74 × 10(-18) and 1.37 × 10(-35), respectively), PCV (P = 3.18 × 10(-19) and 3.96 × 10(-18), respectively), and RAP (P = 0.034 and 2.49 × 10(-18), respectively). Y402H was associated with tAMD (P = 3.00 × 10(-5)) and with PCV (P = 9.73 × 10(-5)), but no association was found with RAP, possibly because of the small sample size and the rare minor allele. The risk allele contribution of A69S was stronger for RAP than for tAMD or PCV and was stronger for tAMD than for PCV.

CFH Y402H is associated with AMD, tAMD, and PCV, whereas I62V is associated with all three subtypes. ARMS2 A69S has a strong association with all three subtypes, with the association being strongest for RAP and weakest for PCV. PCV and RAP may thus be subtypes of AMD that are genetically distinct from tAMD.