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4G/5G polymorphism and haplotypes of SERPINE1 in atherosclerotic diseases of coronary arteries

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: https://doi.org/10.1160/TH09-10-0702
Issue: 2010: 103/6 (June) pp. 1109–1281
Pages: 1170-1180

4G/5G polymorphism and haplotypes of SERPINE1 in atherosclerotic diseases of coronary arteries

Online Supplementary Material

W. Koch (1), M. Schrempf (1), A. Erl (1), J. C. Mueller (2), P. Hoppmann (1), A. Schömig (1), A. Kastrati (1)

(1) Deutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany; (2) Max Planck Institute for Ornithology, Department of Behavioural Ecology and Evolutionary Genetics, Starnberg (Seewiesen), Germany

Keywords

Meta-analysis, Coronary artery disease, myocardial infarction, plasminogen activator inhibitor-1, genetic risk

Summary

We assessed the association between common variation at the SERPINE1 (PAI1) locus and myocardial infarction (MI). Haplotype-tagging polymorphisms, including the 4G/5G deletion/insertion polymorphism and seven single nucleotide polymorphisms, were analysed in a German sample containing 3,657 cases with MI and 1,211 controls. The association between the 4G/5G polymorphism and MI was examined in a meta-analysis of data extracted from 32 studies (13,267 cases/14,716 controls). In addition, the relation between the 4G/5G polymorphism and coronary diseases, comprising MI, coronary artery disease, coronary heart disease, or the acute coronary syndrome, was assessed in a combined analysis enclosing 43 studies (17,278 cases/18,039 controls). None of the tagging polymorphisms was associated with MI in the present sample (p ≤ 0.34). The adjusted odds ratio (OR) for 4G allele carriers was 1.02 (95% confidence interval [CI] 0.87–1.19) compared to the 5G5G genotype. None of 13 common (frequency >1.0%) 8-marker haplotypes was related to the risk of MI. In a meta-analysis specifically addressing the association with MI, no elevated risk was found in the carriers of the 4G allele (OR 1.07, 95% CI 0.99–1.16; p = 0.11). A more general combined analysis of coronary diseases showed a marginally increased risk in 4G allele carriers (OR 1.08, 95% CI 1.00–1.16; p = 0.044). In essence, tagging polymorphisms, including the 4G/5G polymorphism, and common haplotypes of the SERPINE1 gene region were not associated with MI in a German sample, and no compelling evidence was obtained for a relationship of the 4G/5G polymorphism to MI and coronary atherosclerosis in a meta-analysis.

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