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 L. Klein

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


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
StatePublished - Aug 4 2008

ASJC Scopus subject areas

  • Ophthalmology


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