Abstract | BACKGROUND: Recent advances in high-throughput genomics technology have expanded our ability to catalogue allelic variants in large sets of candidate genes related to premature coronary artery disease. METHODS AND RESULTS: A total of 398 families were identified in 15 participating medical centers; they fulfilled the criteria of myocardial infarction, revascularization, or a significant coronary artery lesion diagnosed before 45 years in men or 50 years in women. A total of 62 vascular biology genes and 72 single-nucleotide polymorphisms were assessed. Previously undescribed variants in 3 related members of the thrombospondin protein family were prominent among a small set of single-nucleotide polymorphisms that showed a statistical association with premature coronary artery disease. A missense variant of thrombospondin 4 (A387P) showed the strongest association, with an adjusted odds ratio for myocardial infarction of 1.89 (P=0.002 adjusted for covariates) for individuals carrying the P allele. A variant in the 3' untranslated region of thrombospondin-2 (change of thymidine to guanine) seemed to have a protective effect against myocardial in individuals homozygous for the variant (adjusted odds ratio of 0.31; P=0.0018). A missense variant in thrombospondin-1 (N700S) was associated with an adjusted odds ratio for coronary artery disease of 11.90 (P=0.041) in homozygous individuals, who also had the lowest level of thrombospondin-1 by plasma assay (P=0.0019). CONCLUSIONS:
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Authors | E J Topol, J McCarthy, S Gabriel, D J Moliterno, W J Rogers, L K Newby, M Freedman, J Metivier, R Cannata, C J O'Donnell, K Kottke-Marchant, G Murugesan, E F Plow, O Stenina, G Q Daley |
Journal | Circulation
(Circulation)
Vol. 104
Issue 22
Pg. 2641-4
(Nov 27 2001)
ISSN: 1524-4539 [Electronic] United States |
PMID | 11723011
(Publication Type: Journal Article, Multicenter Study)
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Chemical References |
- Thrombospondin 1
- Thrombospondins
- thrombospondin 2
- thrombospondin 4
- Oxidoreductases Acting on CH-NH Group Donors
- Methylenetetrahydrofolate Reductase (NADPH2)
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Topics |
- Adult
- Age of Onset
- Alleles
- Case-Control Studies
- Coronary Angiography
- Coronary Artery Disease
(epidemiology, genetics)
- Coronary Stenosis
(diagnosis, genetics)
- Demography
- Female
- Genetic Predisposition to Disease
- Genetic Testing
- Genotype
- Homozygote
- Humans
- Male
- Methylenetetrahydrofolate Reductase (NADPH2)
- Middle Aged
- Myocardial Infarction
(diagnosis, epidemiology, genetics)
- Odds Ratio
- Oxidoreductases Acting on CH-NH Group Donors
(genetics)
- Polymorphism, Single Nucleotide
(genetics)
- Predictive Value of Tests
- Thrombospondin 1
(genetics)
- Thrombospondins
(genetics)
- United States
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