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

Peter J. Francis, Hong Zhang, Andrew DeWan, Josephine Hoh, Michael Klein

Research output: Contribution to journalArticle

56 Citations (Scopus)

Abstract

Purpose: To estimate the joint effects of single nucleotide polymorphysms (SNPs) in the genes complementfactor 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 rs 10490924 (6.6 kb upstream of HTRA1 in LOC387715/ARMS2) in 333 cases with advanced AMD (choroidal neovascularization [CNVJ 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, rs 10490924 and rsl 120063 8, is D'=0.8 and all four possible haplotypes of the two SNPs were detected in the samples. The allelic association test for rs 11200638 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-dcpendent 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.

Original languageEnglish (US)
Pages (from-to)1395-1400
Number of pages6
JournalMolecular Vision
Volume14
StatePublished - Aug 4 2008

Fingerprint

Macular Degeneration
Serine
Peptide Hydrolases
Nucleotides
Population
Genes
Geographic Atrophy
Choroidal Neovascularization
Linkage Disequilibrium
Haplotypes
Exons
Confidence Intervals
Phenotype

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Joint effects of polymorphisms in the HTRA1, LOC387715/ARMS2, and CFH genes on AMD in a Caucasian population. / Francis, Peter J.; Zhang, Hong; DeWan, Andrew; Hoh, Josephine; Klein, Michael.

In: Molecular Vision, Vol. 14, 04.08.2008, p. 1395-1400.

Research output: Contribution to journalArticle

Francis, Peter J. ; Zhang, Hong ; DeWan, Andrew ; Hoh, Josephine ; Klein, Michael. / Joint effects of polymorphisms in the HTRA1, LOC387715/ARMS2, and CFH genes on AMD in a Caucasian population. In: Molecular Vision. 2008 ; Vol. 14. pp. 1395-1400.
@article{167271c9d0fc4f6cb778319dc9b177c8,
title = "Joint effects of polymorphisms in the HTRA1, LOC387715/ARMS2, and CFH genes on AMD in a Caucasian population",
abstract = "Purpose: To estimate the joint effects of single nucleotide polymorphysms (SNPs) in the genes complementfactor 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 rs 10490924 (6.6 kb upstream of HTRA1 in LOC387715/ARMS2) in 333 cases with advanced AMD (choroidal neovascularization [CNVJ 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, rs 10490924 and rsl 120063 8, is D'=0.8 and all four possible haplotypes of the two SNPs were detected in the samples. The allelic association test for rs 11200638 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-dcpendent 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 = "Francis, {Peter J.} and Hong Zhang and Andrew DeWan and Josephine Hoh and Michael Klein",
year = "2008",
month = "8",
day = "4",
language = "English (US)",
volume = "14",
pages = "1395--1400",
journal = "Molecular Vision",
issn = "1090-0535",

}

TY - JOUR

T1 - Joint effects of polymorphisms in the HTRA1, LOC387715/ARMS2, and CFH genes on AMD in a Caucasian population

AU - Francis, Peter J.

AU - Zhang, Hong

AU - DeWan, Andrew

AU - Hoh, Josephine

AU - Klein, Michael

PY - 2008/8/4

Y1 - 2008/8/4

N2 - Purpose: To estimate the joint effects of single nucleotide polymorphysms (SNPs) in the genes complementfactor 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 rs 10490924 (6.6 kb upstream of HTRA1 in LOC387715/ARMS2) in 333 cases with advanced AMD (choroidal neovascularization [CNVJ 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, rs 10490924 and rsl 120063 8, is D'=0.8 and all four possible haplotypes of the two SNPs were detected in the samples. The allelic association test for rs 11200638 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-dcpendent 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.

AB - Purpose: To estimate the joint effects of single nucleotide polymorphysms (SNPs) in the genes complementfactor 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 rs 10490924 (6.6 kb upstream of HTRA1 in LOC387715/ARMS2) in 333 cases with advanced AMD (choroidal neovascularization [CNVJ 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, rs 10490924 and rsl 120063 8, is D'=0.8 and all four possible haplotypes of the two SNPs were detected in the samples. The allelic association test for rs 11200638 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-dcpendent 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.

UR - http://www.scopus.com/inward/record.url?scp=48749127259&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=48749127259&partnerID=8YFLogxK

M3 - Article

C2 - 18682806

AN - SCOPUS:48749127259

VL - 14

SP - 1395

EP - 1400

JO - Molecular Vision

JF - Molecular Vision

SN - 1090-0535

ER -