Association of the ELOVL4 Gene With Age–Related Maculopathy

Abstract

Abstract: : Purpose: Age–related maculopathy (ARM) is a leading cause of visual impairment in elderly Americans and is recognized as a complex genetic disorder. To address the genetic etiology of ARM we initiated family–based (343 families, 812 individuals) and case–control based (330 individuals) association studies with the elongation of very long chain fatty acids–like 4 (ELOVL4) gene. Methods: A 5bp deletion in exon six was previously reported to be associated with autosomal dominant macular dystrophy. This 5bp deletion was not found in any of our samples, however a missense mutation located 100bp 3’ to this reported deletion was identified using dHPLC and utilized for our study. Results: The ELOVL4 variant was found to be associated with ARM status in our case–control analyses using simulated chisquare (p = 0.0003) and logistic regression after adjusting for age and sex (p = 0.0018) and in our combined family and case control data using a trend test (p = 0.0000). Conclusions: Based on our findings we believe that the ELOVL4 gene may play a role in sporadic and familial age–related maculopathy and adds support for the importance of fatty acid biosynthesis to a healthy retina. Additional analyses including replicate testing and haplotype analyses are being conducted to confirm these findings.

Keywords: age-related macular degeneration • genetics • lipids