Purpose: To study and reveal genetic variation in the elastin gene (ELN) that may be associated with neovascular age-related macular degeneration (AMD) and/or polypoidal choroidal vasculopathy (PCV). Eyes with neovascular AMD and PCV exhibit substantially different structural alterations of the elastic layer in the Bruch's membrane. The hypothesis for the present study was that ELN polymorphisms may play a role in the development of neovascular AMD and PCV and that genetic differences in ELN between these two phenotypes may be a reason for the histopathologic differences. To test these hypotheses, ELN was screened for genetic variation in a Japanese case-control dataset.
Methods: Two hundred eighty-five subjects were enrolled: 78 with neovascular AMD, 103 with PCV, and 104 control. We genotyped five tagged single nucleotide polymorphisms (SNPs) in ELN, and allele, genotype, and haplotype frequency distributions among neovascular AMD, PCV, and control subjects were compared by chi(2) tests.
Results: A common ELN variant was significantly associated with susceptibility to PCV. The age- and sex-adjusted odds ratio was 7.56 for individuals homozygous for the risk allele compared with those carrying no more than one copy of the risk allele. Significantly different distributions were found in allele and haplotype frequencies between neovascular AMD and PCV in this region, but no particular ELN SNPs or haplotypes were significantly associated with neovascular AMD.
Conclusions: The findings implicate ELN as a susceptibility gene for PCV, and suggest that a different pathogenic process may be involved in the phenotypic expression of neovascular AMD and PCV.