Common variants in the complement factor H gene confer genetic susceptibility to central serous chorioretinopathy

Purpose: To investigate whether complement factor H (CFH) gene DNA variants are associated with central serous chorioretinopathy (CSCR).

Design: Cross-sectional study.

Participants: A case-control group of 140 CSCR subjects and 2 different control groups: 934 population-based controls and 335 hospital-based controls.

Methods: Five single-nucleotide polymorphisms (SNPs) in CFH (rs3753394, rs800292, rs2284664, rs1329428, and rs106548) were evaluated for association with CSCR in 2 separate association analyses comparing CSCR subjects with 2 different control groups. Genotyping was performed using TaqMan technology (Applied Biosystems, Foster City, CA).

Main outcome measures: Allele and haplotype frequencies of the 5 variants in the CFH region.

Results: Highly statistically significant associations with CSCR were found for the 5 SNPs. The strongest association was observed with rs1329428 (allelic P = 6.44×10(-6); odds ratio, 1.79; 95% confidence interval [CI], 1.39-2.31, cases vs. population-based controls), which accounted for 35.5% of the population-attributable fraction for CSCR. Consistent with the analysis, rs1329428 showed the strongest disease association (allelic P = 1.00×10(-5); odds ratio, 1.89; 95% CI, 1.42-2.50) in comparing cases with hospital-based controls. The second most strongly associated SNP, rs1065489, was correlated highly with the most strongly associated SNP, rs1329428 (r(2) = 0.77), and their effects could not be distinguished statistically from each other. A conditional logistic regression analysis revealed that the 2 highly correlated SNPs, rs1329428 and rs1065489, account for the association signals detected at the CFH locus.

Conclusions: We identified a novel association between CSCR and common CFH polymorphisms. Our findings support the involvement of CFH in the pathogenesis of CSCR; exploration of the role of CFH could yield important insights into the biological mechanisms underlying CSCR. Our identification of common CFH variants as susceptibility elements for CSCR will open new avenues for research, leading to a better understanding of CSCR pathogenesis and ultimately to the development of improved therapeutic approaches.