Dataset Information

Three major loci involved in age-related macular degeneration are also associated with polypoidal choroidal vasculopathy.

ABSTRACT:

Purpose

To investigate the frequency of variants in 3 major age-related macular degeneration (AMD)-associated loci in patients of European-American descent with polypoidal choroidal vasculopathy (PCV).

Design

Cross-sectional, case-control association study.

Participants

Fifty-five patients with PCV, 368 patients with advanced AMD, and 368 age-matched and ethnically matched unaffected controls of European-American descent.

Methods

Association analysis of allele and genotype frequencies, determined by TaqMan assays, was performed for the following haplotype-tagging single nucleotide polymorphisms (htSNPs): risk alleles in the complement factor H (CFH) gene (Y402H and IVS14) in the ARMS2/HTRA1 locus on 10q26 (A69S) and protective alleles in CFH (IVS1 and IVS6) and in the complement factor B/complement component C2 (CFB/C2) locus (IVS10 and H9L).

Main outcome measures

Allele and genotype frequencies of the htSNPs in the CFH, CFB/C2, and ARMS2/HTRA1 loci.

Results

Four AMD-associated haplotype-tagging alleles (rs547154, rs1061170, rs1410996, rs10490924) in the 3 major loci, CFH, CFB/C2, and ARMS2/HTRA1, also were statistically significantly associated with the PCV phenotype (P<0.05). Three other alleles from the same loci (rs4151667, rs529825, rs3766404) showed a trend toward association (P<0.2) but did not reach statistical significance, possibly because of the combined effects of a relatively small sample size and low minor allele frequency in the screened populations.

Conclusions

The PCV phenotype in Caucasian patients is associated with the major alleles/genotypes in the AMD-associated loci, suggesting that PCV and AMD are genetically similar in the tested loci.

SUBMITTER: Lima LH

PROVIDER: S-EPMC2901561 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Publications

Three major loci involved in age-related macular degeneration are also associated with polypoidal choroidal vasculopathy.

Lima Luiz H LH Schubert Carl C Ferrara Daniela C DC Merriam Joanna E JE Imamura Yutaka Y Freund K Bailey KB Spaide Richard F RF Yannuzzi Lawrence A LA Allikmets Rando R

Ophthalmology 20100408 8

<h4>Purpose</h4>To investigate the frequency of variants in 3 major age-related macular degeneration (AMD)-associated loci in patients of European-American descent with polypoidal choroidal vasculopathy (PCV).<h4>Design</h4>Cross-sectional, case-control association study.<h4>Participants</h4>Fifty-five patients with PCV, 368 patients with advanced AMD, and 368 age-matched and ethnically matched unaffected controls of European-American descent.<h4>Methods</h4>Association analysis of allele and ge ...[more]

PMID: 20378180

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Project description:PurposeA nonsynonymous coding variant in the manganese superoxide dismutase (SOD2) gene (V16A, rs4880) has been implicated in neovascular age-related macular degeneration (AMD). However, the findings have been inconsistent. Two studies in Japanese populations reported an opposite direction of association of the same allele at the V16A variant, whereas one study in a Northern Irish population found no effect of the variant on the risk of developing neovascular AMD. To address these apparently contradictory reports, we validated the association in a Japanese population.MethodsIn a Japanese population, we genotyped the V16A variant in 116 neovascular AMD patients, 140 polypoidal choroidal vasculopathy (PCV) patients, and 189 control participants. This association was also tested in a population of PCV participants to avoid variable findings across studies due to underlying sample heterogeneity and because disease phenotype was not well described in previous studies. We analyzed a tagging single nucleotide polymorphism (SNP) in addition to the V16A variant to capture all common SOD2 variations verified by the HapMap project. Genotyping was conducted using TaqMan technology. Associations were tested using single-SNP and haplotype analyses as well as a meta-analysis of the published literature. Population stratification was also evaluated in our study population.ResultsWe found no detectable association of the V16A variant or any other common SOD2 variation with either neovascular AMD or PCV, as demonstrated by both single-SNP and haplotype analyses. Population structure analyses precluded stratification artifacts in our study cohort. A meta-analysis of the association between the V16A variant and neovascular AMD also failed to detect a significant association.ConclusionsWe found no evidence to support the role of any common SOD2 variations including the V16A variant in the susceptibility to neovascular AMD or PCV. Our study highlights the importance and difficulty in replicating genetic association studies of complex human diseases.

Dataset Information

Three major loci involved in age-related macular degeneration are also associated with polypoidal choroidal vasculopathy.

Purpose

Design

Participants

Methods

Main outcome measures

Results

Conclusions

Publications

Three major loci involved in age-related macular degeneration are also associated with polypoidal choroidal vasculopathy.

Similar Datasets

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