Thrombospondin-4-Ala387Pro polymorphism is not associated with vascular function and risk of coronary heart disease in US men and women [4]

Thrombosis and Haemostasis (Impact Factor: 4.98). 04/2006; 95(3):589-90. DOI: 10.1267/THRO06030589
Source: PubMed
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    ABSTRACT: The thrombospondins are a 5-member gene family that mediate cell-cell and cell-matrix interactions. The thrombospondins are either trimers or pentamers, and their functions depend on their abilities to interact with numerous extracellular ligands and cell surface receptors through the multiple domains that compose each subunit. Recent genetic studies have indicated associations of particular single nucleotide polymorphisms in 3 of the 5 thrombospondins with cardiovascular disease. This observation has stimulated efforts to understand how the thrombospondins influence cardiovascular pathology, to dissect how the individual polymorphisms alter the structure and function of the parent thrombospondin molecules, and to replicate the genetic data in different patient populations. This review seeks to summarize current information that has emerged on each of these fronts.
    Preview · Article · Oct 2007 · Arteriosclerosis Thrombosis and Vascular Biology
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    ABSTRACT: A role of thrombospondins (TSPs) in atherosclerosis and thrombosis was suggested by associations of single nucleotide polymorphisms in the genes coding for TSP-1 (rs2228262; Asn700Ser), TSP-2 (rs8089; 3' untranslated region), and TSP-4 (rs1866389; Ala387Pro) with myocardial infarction (MI). However, these findings were not consistently confirmed in replication studies. We determined the genotypes related to these polymorphisms in a large case-control sample of MI and performed a meta-analysis of data obtained in the present sample and available from prior studies that included Europeans or Americans of European origin. In the population examined here, the carriers of the minor allele of the polymorphism in the TSP-2 gene (GG and TG genotypes) had a mildly statistically significant higher risk of MI than the homozygous carriers of the major allele (TT genotype) [adjusted odds ratio (OR) 1.19; 95% confidence interval (CI), 1.02 to 1.39]. In similar comparisons, no associations of the polymorphisms in the TSP-1 (adjusted OR 1.12; 95% CI, 0.93 to 1.35) and TSP-4 (adjusted OR 0.99; 95% CI, 0.85 to 1.16) genes with MI were observed. The meta-analysis included 6388 (TSP-1), 4930 (TSP-2), and 6978 (TSP-4) cases. None of the polymorphisms was found to be linked with the risk of MI. Thus, despite associations in certain individual studies, the synthesis of available evidence did not suggest that the TSP polymorphisms included in this study were associated with MI.
    No preview · Article · May 2008 · Human Molecular Genetics
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    ABSTRACT: In addition to its major structural elements, extracellular matrix contains a number of factors that are important for orchestrating developmental morphogenesis, maintaining tissue homeostasis in adults, and regenerating tissue following injury. Several proteins that serve these functions share a complex modular structure that enables them to interact with specific components of the matrix while engaging specific cell surface receptors through which they control cell behavior. These have been named matricellular proteins. Matricellular proteins, including the thrombospondins, some thrombospondin-repeat superfamily members, tenascins, SPARC, CCN proteins, and SIBLING proteins, are increasingly recognized to play important roles in inherited disorders, responses to injury and stress, and the pathogenesis of several chronic diseases of aging. Improved understanding of the functions and mechanisms of action of matricellular proteins is beginning to yield novel therapeutic strategies for prevention or treatment of these diseases.
    No preview · Chapter · Feb 2011
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