Candidate gene analysis suggests a role for fatty acid biosynthesis and regulation of the complement system in the etiology of age-related maculopathy
Open Access
- 1 June 2005
- journal article
- research article
- Published by Oxford University Press (OUP) in Human Molecular Genetics
- Vol. 14 (14), 1991-2002
- https://doi.org/10.1093/hmg/ddi204
Abstract
Age-related maculopathy (ARM) is a leading cause of visual impairment in elderly Americans and is a complex genetic disorder. Hypothesized pathways for the etiology of ARM include cholesterol and lipoprotein metabolism and transport, extracellular matrix integrity, oxidative stress and inflammatory/immunologic processes. This study investigates 21 polymorphisms within 15 candidate genes whose products function within these pathways by performing family and case–control genetic association studies using clearly affected familial cases (n=338 families, 796 individuals), clearly affected, unrelated sporadic cases (n=196) and clearly unaffected, unrelated controls (n=120). Two genes demonstrated significant association with ARM status. A Met299Val variant in the elongation of very long chain fatty acids-like 4 (ELOVL4) gene was significantly associated with ARM in the case–control allele (P=0.001), case–control genotype (P=0.001) and case–control family (PCFH) gene was also significantly associated with ARM in the case–control allele (PPPCFH variant appears to play a role in exudative and atrophic disease, whereas the ELOVL4 variant may play a greater role in exudative disease in our population. These results support a potential role for multiple pathways in the etiology of ARM, including pathways involved with fatty acid biosynthesis and the complement system.Keywords
This publication has 69 references indexed in Scilit:
- Age-Related Maculopathy: A Genomewide Scan with Continued Evidence of Susceptibility Loci within the 1q31, 10q26, and 17q25 RegionsAmerican Journal of Human Genetics, 2004
- Causes and Prevalence of Visual Impairment Among Adults in the UnitedStatesAmerican Journal of Ophthalmology, 2004
- Linkage analysis for age-related macular degeneration supports a gene on chromosome 10Q26American Journal of Ophthalmology, 2004
- Age-Related Macular Degeneration: A High-Resolution Genome Scan for Susceptibility Loci in a Population Enriched for Late-Stage DiseaseAmerican Journal of Human Genetics, 2004
- Dissection of Genomewide-Scan Data in Extended Families Reveals a Major Locus and Oligogenic Susceptibility for Age-Related Macular DegenerationAmerican Journal of Human Genetics, 2004
- A Genomewide Scan for Age-Related Macular Degeneration Provides Evidence for Linkage to Several Chromosomal RegionsAmerican Journal of Human Genetics, 2003
- Age-Related Macular Degeneration—a Genome Scan in Extended FamiliesAmerican Journal of Human Genetics, 2003
- Genetic influence on early age-related maculopathyOphthalmology, 2002
- Age-related maculopathy: an expanded genome-wide scan with evidence of susceptibility loci within the 1q31 and 17q25 regionsAmerican Journal of Ophthalmology, 2001
- Age-related Macular DegenerationAmerican Journal of Ophthalmology, 1998