ERCC6 and the Risk of Age-related Macular Degeneration in two Study Populations from the Netherlands

Abstract

Purpose: : To study genetic associations between ERCC6 and Age-related Macular Degeneration (AMD).

Methods: : We investigated associations between the polymorphism ERCC6 rs3793784: C>G (c.-6530C>G) and AMD in two independent Netherlands study groups: the population-based prospective Rotterdam Study (over 7000 participants) and an independent case-control group of 357 non-familial AMD cases and 172 controls. We also determined ERCC6 expression levels in healthy human retinal pigment epithelium (RPE) cells and those from early AMD eyes.

Results: : The ERCC6 promoter SNP rs3793784: C>G conferred no significant association in the prevalent analyses of the Rotterdam Study and the case-control study. A small but significant increase in risk for late AMD was seen in incident cases. The pooled data yielded an odds ratio of 1.39 (95% CI: 1.02-1.89). The synergy index revealed no significant interaction between ERCC6 and smoking, CFH Y402H or LOC387715 A69S related to AMD predisposition. In contrast with previous findings, we could not find increased ERCC6 expression in RPE cells from early AMD eyes.

Conclusions: : Although no consistent relationship was observed in our two study groups, the overall result of the pooled data represents the first independent confirmation of the genetic association between ERCC6 and AMD (Tuo et al . 2006, Proc. Natl. Acad. Sci. USA). This association cannot be explained by higher expression of ERCC6 in RPE cells from eyes with early AMD.

Keywords: age-related macular degeneration • genetics • gene/expression