Candidate Genes Study in Aged-Related Macular Degeneration (amd) in Patients Who Do Not Carry the at-Risk Alleles for Cfh and Loc387715 Genes

Abstract

Purpose: : Aged-related Macular Degeneration (AMD) is a frequent and multifactorial disease, where genetic variants confer a major disease risks. The aim of the present work was to identify novel genetic factors predisposing to AMD by the study of a group of patients and controls who did not carry risk-alleles for CFH and LOC387715 genes.

Methods: : 1255 AMD patients and 301 controls over 55 years old were recruited in 3 French ophthalmologic centers. A complete ophthalmologic examination was performed to classify the AMD. Informations about the medical and familial history, cardiovascular risk factors, and diet were collected. The cohort of patients and controls was first genotyped for the Y402H polymorphism of CFH gene and the rs10490924 of the LOC387715 gene to select individuals harbouring wild-type alleles for both genes. Subsequently, candidate genes were selected by virtue of their localisation and/or their function. SNPs with the highest informative content respectively located in the apolipoprotein J, OSBP2, vitronectin C3 and CX3CR1 encoding genes were genotyped.

Results: : Sixty-four AMD patients and 77 controls were found double homozygous for wild-type alleles of both CFH and LOC387715 in the whole cohort. The candidate gene analysis in these individuals showed no statistically significant differences in the repartition of genotypes between AMD patients and controls.

Conclusions: : Different pathways are involved in the pathophysiology of the disease : inflammation cascade, lipid regulation... This study shows that different genes, some of which initially associated to AMD, seems to not be involved in AMD, independantly to CFH and LOC387715 genes.This study is still in progress in order to identify novel genetic factors for AMD, which could help to a better knowledge of the pathophysiology of the disease.

Keywords: age-related macular degeneration • genetics • candidate gene analysis