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Polymorphic variants in tenascin-C (TNC) are associated with atherosclerosis and coronary artery disease
- Source :
- Human genetics. 129(6)
- Publication Year :
- 2010
-
Abstract
- Tenascin-C (TNC) is an extracellular matrix protein implicated in biological processes important for atherosclerotic plaque development and progression, including smooth muscle cell migration and proliferation. Previously, we observed differential expression of TNC in atherosclerotic aortas compared with healthy aortas. The goal of this study was to investigate whether common genetic variation within TNC is associated with risk of atherosclerosis and coronary artery disease (CAD) in three independent datasets. We genotyped 35 single nucleotide polymorphisms (SNPs), including 21 haplotype tagging SNPs, in two of these datasets: human aorta tissue samples (n = 205) and the CATHGEN cardiovascular study (n = 1,325). Eleven of these 35 SNPs were then genotyped in a third dataset, the GENECARD family study of early-onset CAD (n = 879 families). Three SNPs representing a block of linkage disequilibrium, rs3789875, rs12347433, and rs4552883, were significantly associated with atherosclerosis in multiple datasets and demonstrated consistent, but suggestive, genetic effects in all analyses. In combined analysis rs3789875 and rs12347433 were statistically significant after Bonferroni correction for 35 comparisons, p = 2 × 10(-6) and 5 × 10(-6), respectively. The SNP rs12347433 is a synonymous coding SNP and may be biologically relevant to the mechanism by which tenascin-C influences the pathophysiology of CAD and atherosclerosis. This is the first report of genetic association between polymorphisms in TNC and atherosclerosis or CAD.
- Subjects :
- Adult
Male
Linkage disequilibrium
Smooth muscle cell migration
Genotype
Single-nucleotide polymorphism
Coronary Artery Disease
Polymorphism, Single Nucleotide
Linkage Disequilibrium
Article
Coronary artery disease
Genetics
medicine
SNP
Humans
Genetics (clinical)
Genetic association
biology
Tenascin C
Haplotype
Tenascin
Middle Aged
medicine.disease
Atherosclerosis
Phenotype
Haplotypes
biology.protein
Female
Subjects
Details
- ISSN :
- 14321203
- Volume :
- 129
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Human genetics
- Accession number :
- edsair.doi.dedup.....4d42782e1e222acdfa6455ef9aed692f