Joint effects of polymorphisms in the HTRA1, LOC387715/ARMS2, and CFH genes on AMD in a Caucasian population.

Full Abstract

PURPOSE: To estimate the joint effects of single nucleotide polymorphisms (SNPs) in the genes complement factor H (CFH), HtrA serine peptidase 1 (HTRA1), and age-related maculopathy susceptibility 2 (LOC387715/ARMS2) in a Caucasian age related macular degeneration (AMD) case-control cohort. METHODS: We genotyped three SNPs, rs1061170 (exon 9, CFH), rs11200638 (HTRA1 promoter, -512 bp), and rs10490924 (6.6 kb upstream of HTRA1 in LOC387715/ARMS2) in 333 cases with advanced AMD (choroidal neovascularization [CNV] and geographic atrophy) and 171 age-matched examined controls. Association tests were performed for individual SNPs and jointly with the CFH SNP Y402H. Analyses for interaction were also performed. RESULTS: The linkage disequilibrium measure for two SNPs on 10q26, rs10490924 and rs11200638, is D'=0.8 and all four possible haplotypes of the two SNPs were detected in the samples. The allelic association test for rs11200638 on the promoter of HTRA1 yielded p-values less than 10(-10) for geographic atrophy, less than 10(-16) for neovascularization, and less than 10(-19) for the pooled phenotypes (with an odds ration [OR] of 3.973; 95% confidence interval [CI] 2.928, 5.390). Disease risk is conferred in a dosage-dependent fashion. Similar figures were observed for the LOC387715/ARMS2 SNP. No interaction was detected between either between the 10q26 SNPs or the CFH SNP. CONCLUSIONS: This is the first analysis to show that the two 10q26 SNPs are not in complete linkage disequilibrium. Our studies however show that both the HTRA1 and LOC387715/ARMS2 SNP appear to contribute equally to disease risk (both geographic atrophy and choroidal neovascularization) with no evidence of interaction with CFH.

Author information

Author/s: Francis, Peter J (PJ); Zhang, Hong (H); Dewan, Andrew (A); Hoh, Josephine (J); Klein, Michael L (ML);

Affiliation: Macular Degeneration Center, Casey Eye Institute, Oregon Health & Science University, Portland, OR, USA.

Grants: R01-EY015771 (Agency:NEI NIH HHS) ; R01-EY12203 (Agency:NEI NIH HHS) ; R21-EY018127 (Agency:NEI NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Molecular vision (Mol Vis), published in United States. (Language: eng)

Reference: 2008-; vol 14 (issue ) : pp 1395-400

Dates: Created 2008/08/06; Completed 2008/09/24; Revised 2008/11/20;

PMID: 18682806, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Haplotypes
Humans
Macular Degeneration - genetics
Middle Aged
Odds Ratio
Phenotype
Polymorphism, Single Nucleotide - genetics
Proteins - genetics
Serine Endopeptidases - genetics

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: ARMS2 protein, human (0) ; Proteins (0) ; Complement Factor H (80295-65-4) ; HtrA1 protein, human (EC 3.4.21.-) ; Serine Endopeptidases (EC 3.4.21.-)

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