Abstract
Purpose::
Age-related macular degeneration (AMD) is a common complex disorder that affects the central region of the retina and is the leading cause of legal blindness in Caucasian Americans aged >65 years. Along with the Y402H variant of the complement factor H gene (CFH) on chromosome 1q32, several other genetic variants within 10q26 have been identified as susceptibility loci for AMD. However, the exact susceptibility variant within 10q26 is currently unknown.
Methods::
We compared two previously proposed SNPs, rs10490924 in LOC387715 and rs11200638 in HTRA1 (r2=0.93), by performing an association analysis in two unrelated datasets, one case-control one family-based. The case-control dataset included 644 cases and 265 controls and was analyzed by logistic regression using an additive model with adjustment for age and sex. The family-based dataset included cases with at least one sampled relative (n = 205 families), and were analyzed for association using the APL (Association in the Presence of Linkage) statistic.
Results::
In the case-control dataset, both variants had strong association with AMD (P < 0.0001), with similar odds ratios (rs10490924: 2.13 (95% CI 1.65-2.75); rs11200638: 2.00 (95% CI 1.56-2.57)). Using only cases with neovascularization (n=405) and controls with no drusen (n=193), the results were similar but the odds ratios stronger (rs10490924: 2.98 (95% CI 2.14-4.16); rs11200638: 2.80 (95% CI 2.03-3.88)). These data suggest the risk may be stronger for neovascular AMD. The association results in the family-based dataset, although not as strong, confirmed these effects (rs11200638 (P = 0.02), rs10490924 (P = 0.05).
Conclusions::
These data do not allow us to differentiate between the potential roles of LOC387715 and HTRA1 in AMD.
Keywords: age-related macular degeneration • genetics