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

Werner Koch; Matthias Schrempf; Anna Erl; Jakob C. Mueller; Petra Hoppmann; Albert Schömig; Adnan Kastrati

doi:10.1160/TH09-10-0702

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2010; 103(06): 1170-1180
DOI: 10.1160/TH09-10-0702

Blood Coagulation, Fibrinolysis and Cellular Haemostasis

Schattauer GmbH

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

Werner Koch

¹Deutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

,

Matthias Schrempf

¹Deutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

,

Anna Erl

¹Deutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

,

Jakob C. Mueller

²Max Planck Institute for Ornithology, Department of Behavioural Ecology and Evolutionary Genetics, Starnberg (Seewiesen), Germany

,

Petra Hoppmann

¹Deutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

,

Albert Schömig

¹Deutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

,

Adnan Kastrati

¹Deutsches Herzzentrum München and 1. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität München, Munich, Germany

› Author Affiliations

Abstract

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.

Keywords

Myocardial infarction - coronary artery disease - genetic risk - plasminogen activator inhibitor-1 - meta-analysis

Full Text

References

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