RGD Reference Report - Joint effects of polymorphisms in the HTRA1, LOC387715/ARMS2, and CFH genes on AMD in a Caucasian population. - Rat Genome Database

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

Authors: Francis, PJ  Zhang, H  Dewan, A  Hoh, J  Klein, ML 
Citation: Francis PJ, etal., Mol Vis. 2008 Aug 4;14:1395-400.
RGD ID: 7394694
Pubmed: PMID:18682806   (View Abstract at PubMed)
PMCID: PMC2493023   (View Article at PubMed Central)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Choroidal Neovascularization  IAGP 7394694DNA:snp:promoter:g.-625G>A (rs11200638) (human)RGD 
Choroidal Neovascularization  ISOHTRA1 (Homo sapiens)7394694; 7394694DNA:snp:promoter:g.-625G>A (rs11200638) (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Abnormal morphology of the choroidal vasculature  IAGP 7394694DNA:snp:promoter:g.-625G>A (rs11200638) RGD 
Objects Annotated

Genes (Rattus norvegicus)
Htra1  (HtrA serine peptidase 1)

Genes (Mus musculus)
Htra1  (HtrA serine peptidase 1)

Genes (Homo sapiens)
HTRA1  (HtrA serine peptidase 1)


Additional Information