Association of Genes and Environment to Progression of Age- Related Macular Degeneration

Abstract

Purpose: : We evaluated impact of genetic variants and systemic risk factors on AMD progression.

Methods: : Clinical, genotype and environmental risk factor data on the subset of patients with AMD Grades 2, 3 and 4 were analyzed. Evidence of progression or non progression of AMD grade was analyzed by evaluating serial fundus photographs. Of 650 AMD patients ascertained, 67 had intermediate AMD in one or both eyes. Of these, 36 had fundus photos available at multiple time points. Progressors (P) were defined as those who advanced by one or more grade. We tested unilateral and bilateral progression of AMD for univariate association with CFH Y402H, ARMS2 A69S, CFB R32Q, C3 R102G, mito4917, age at initial exam, gender, smoking, and body mass index (BMI) using logistic regression.

Results: : Group 1 (26 patients) had bilateral intermediate AMD, and Group 2 (10 patients) had intermediate in one eye and neovascular AMD in the fellow eye. Average followup was 2.4 years. Group 1 had 14 non progressors (NP), 5 unilateral P and 7 bilateral P. Group 2 had 6 NP and 4 P. The mito4917 risk allele was found in 50.0% of bilateral progressors, but in only 7.6% of non-progressors (p=0.06) in Group 1. No other gene or environmental risk factors showed significant association with progression in either Group.

Conclusions: : In this preliminary analysis, mito4917 is a risk allele for progression in patients with bilateral intermediate AMD. Data from a larger dataset is currently being collated.

Keywords: age-related macular degeneration • gene screening • clinical (human) or epidemiologic studies: risk factor assessment