Coding and Noncoding Variants in the CFH Gene, Including rs1410996, Influence the Risk of Age-Related Macular Degeneration in a Japanese Population

Abstract

Purpose:: Ethnic variation has been reported in age-related macular degeneration (AMD)-associated Y402H polymorphism in complement factor H (CFH).This variation is evident in the Japanese population. Recently a strong association between a novel SNP (rs1410996) in the CFH gene and AMD has been identified in Caucasian populations of predominantly European descent (Li M, et al. Science 2006; Maller J, et al. Science 2006). The present study investigates whether four coding and noncoding variants of the CFH gene, including rs1410996, are associated with AMD in native, unrelated Japanese patients.

Methods:: A total of 190 patients with AMD and 135 control subjects without AMD were recruited for this study. Four SNPs (rs2274700, rs1410996, rs800292, rs1061170) in the CFH gene were assessed using a TaqMan assay.

Results:: The noncoding SNP (rs1410996) was associated with a significant risk of developing AMD in a Japanese population (p=2.4x10^-5, OR(95%CI); 1.98(1.44-2.72)). Significant association was also noted between a coding variant (rs800292, I62V) and AMD (p=8.6x10^-6, OR(95%CI); 2.10(1.51-2.92)). In contrast, the Y402H variant showed no significant association with AMD (p=0.10). Two common haplotypes also demonstrated significant association with AMD (p=1.28x10^-5, 1.11x10^-3).

Conclusions:: Although the Y402H variant was not significantly associated with AMD, other coding and noncoding variants in the CFH gene including rs1410996 moderately influenced the risk of AMD in a Japanese population.

Keywords: age-related macular degeneration • genetics