Complement Factor H (CFH) and Apolipoprotein E (APOE) Gene Polymorphisms Are Risk Factors for Exsudative AMD

Abstract

Purpose: : Age related macular degeneration (AMD) is a leading cause of visual impairment in industrialized countries. In a case control study, we screened polymorphisms of the Apo E gene, and of the recently identified complement factor H (CFH) susceptibility gene. Polymorphisms at these gene loci have been described as major genetic risk factors for AMD in different human populations. The aim of this study was to assess these gene polymorphisms in a French population specifically affected with exsudative AMD.

Methods: : A complete ophthalmological examination including best corrected visual acuity measurement, fundus examination and fluorescein angiography (FA) was performed 141 patients with exsudative AMD. AMD patients were classified in two subgroups: 1/ sporadic cases (n=60, mean age 74.9±5.7), 2/ familial cases (n=81, mean age 74.0±9.4). Genotypes in AMD patients were compared with healthy age and sex matched controls (n= 91, mean age 74.6±6.3). For CFH Y402H polymorphism, genotyping was performed by sequencing of PCR products including the polymorphism. For Apo E genotyping, allele discrimination was performed on genomic DNA extracted from blood leucocytes, by real–time PCR (ABI^® assay on demand) on a mx3000 Stratagene^® apparatus.

Results: : Genotypic distribution of the Y402H polymorphism were significantly different between sporadic cases versus controls (Chi² = 14.48 [2 df], p<0.0007) and between familial cases versus controls (Chi² = 23.78 [2 df], p<0.0001). In familial cases, the OR for AMD risk were 3.6 CI 95% [1.7–7.6] for CT heterozygotes and OR= 8.0 CI 95% [3.2–19.8] for CC homozygotes. Genotypic distribution for Apo E polymorphisms were also significantly different between cases and control cases (Chi² = 4.7 [1 df], p<0.05). The OR for AMD risk were 1.74 CI 95% [0.68–4.44] for the Apo E2 carriers, and 0.48 CI 95% [0.22–1.3] for the Apo E4 carriers.

Conclusions: : Here we confirm the involvement of the CFH Y402H polymorphism, and of the Apo E polymorphisms as risk factors for exsudative AMD in a French population. Screening for candidate genes appears of importance to understand biological processes underlying AMD and to predict individual risk of AMD.

Keywords: genetics • age-related macular degeneration • inflammation