Coding variant I62V in the complement factor H gene is strongly associated with polypoidal choroidal vasculopathy.

Area of Science:

• Ophthalmology
• Genetics
• Immunology

Background:

• Polypoidal choroidal vasculopathy (PCV) is a common subtype of age-related macular degeneration.
• The complement system, particularly complement factor H (CFH), is implicated in the pathogenesis of various ocular diseases.

Purpose of the Study:

• To investigate the association between variants in the complement factor H (CFH) gene and the risk of developing polypoidal choroidal vasculopathy (PCV).

Main Methods:

• A case-control study was conducted with 130 PCV patients and 173 unrelated controls from a Japanese population.
• Genotyping of 12 tag single nucleotide polymorphisms (SNPs) in the CFH gene, including rs800292 (I62V) and rs1061170 (Y402H), was performed using TaqMan technology.
• Association analyses of allele and haplotype frequencies were conducted.

Main Results:

• A significant association between the CFH gene region and PCV was observed.
• The strongest association was found at the rs800292 (I62V) variant (P = 1.7 x 10(-7)).
• Conditional analyses indicated that the I62V variant fully accounts for the observed association signals across the examined CFH SNPs due to linkage disequilibrium.

Conclusions:

• The complement pathway plays a significant role in the pathogenesis of PCV.
• The nonsynonymous CFH variant I62V is a strong candidate for a causal polymorphism contributing to PCV development.