The Loc387715 Gene Determines Risk for Development of Atrophic and Exudative Age–Related Macular Degeneration

Abstract

Purpose: : This is a retrospective case–control study to determine if a susceptibility gene for age–related macular degeneration (AMD) on chromosome 10q26 (LOC387715) determines risk for development of mild/early (grade 3), atrophic (GA, grade 4) and exudative (grade 5) age–related macular degeneration (AMD).

Methods: : To determine if the LOC387715 gene had any effect on determining risk for development of mild/early AMD, GA or exudative AMD in a case–control data set of 730 AMD cases and 251 controls, the rs10490924 single nucleotide polymorphism (SNP) was tested for association, separating grades and analyzing them independently against the controls. Odds ratios were calculated using standard logistic regression models (SAS version 8.2). The outcome variable was AMD affection status and genotypes were coded according to a log–additive model.

Results: : The data set contained 730 age–related macular degeneration (AMD) cases (grades 3/4/5) and 251 controls (grades 1/2). There were 458 grade–5 individuals, 122 grade–4, 150 grade–3, 64 grade–2, and 187 grade–1 individuals. There was significant association with AMD when comparing grades 3, 4, and 5 versus the controls. The highest odds ratio was obtained when analyzing the grade–5 cases versus the grade–1 controls (OR = 3.193, P < 0.0001).

Conclusions: : A coding change in the LOC387715 gene is the second major AMD susceptibility allele identified. Its effect on AMD is statistically independent of the CFH gene, and of similar magnitude as the effect of T1277C. We estimate that LOC387715 and CFH together account for 65% of AMD. Our results indicate that this gene increases the risk of developing all forms of AMD, including mild/early AMD (grade 3), atrophic (GA, grade 4) and neovascular (grade 5) disease.

Keywords: age-related macular degeneration • genetics