The <i>LOC387715 </i>Gene, Smoking, Body Mass Index, Environmental Associations with Advanced Age-Related Macular Degeneration

<i>Background and Aims:</i> Age-related macular degeneration (AMD) is the leading cause of blindness in the Western World. It is now evident that both genetic and environmental factors contribute to disease susceptibility. We tested the hypotheses that (a) a common coding SNP in the <i>LOC387715 </i>gene is associated with advanced AMD (geographic atrophy or choroidal neovascularization), and (b) that modifiable environmental exposures alter AMD susceptibility associated with this SNP. <i>Methods:</i> A case-control association analysis was performed on participants (530 advanced AMD cases and 280 controls) ascertained as part of the multi-center Age-Related Eye Disease Study. AMD status was determined by the reading center from fundus photographs using the AREDS AMD grading categorization. Environmental risk factor exposure data was collected from participants whose DNA was also genotyped for the <i>LOC387715</i> gene SNP rs10490924. Multivariate logistic regression analyses were performed. <i>Results and Conclusions:</i> The number of risk alleles at the <i>LOC387715</i> SNP was associated with advanced AMD, with odds ratios (OR) = 3.0 (95% confidence interval (CI) 2.1–4.3) for the GT heterozygous genotype and OR = 12.1 (5.6–26.5) for the homozygous TT risk genotype, after controlling for demographic and behavioral risk factors. The <i>LOC387715</i> SNP was associated with both forms of advanced AMD. Current cigarette smoking and body mass index were independently related to AMD, controlling for genotype. However, there was no statistical interaction between <i>LOC387715</i> genotype and smoking with regard to advanced AMD development.