Human Molecular Genetics Advance Access originally published online on January 4, 2008
Human Molecular Genetics 2008 17(8):1120-1126; doi:10.1093/hmg/ddn001
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Polymorphisms in thrombospondin genes and myocardial infarction: a case–control study and a meta-analysis of available evidence
1 Deutsches Herzzentrum München, 80636 Munich, Germany 2 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, 81675 Munich, Germany
* To whom correspondence should be addressed at: Deutsches Herzzentrum München, Lazarettstrasse 36, 80636 Munich, Germany. Tel: +49 8912182601; Fax: +49 8912183053; Email: wkoch{at}dhm.mhn.de
Received November 19, 2007; Accepted January 2, 2008
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.