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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:2250.)
© 2007 American Heart Association, Inc.

Thrombosis

Association of Plasminogen Activator Inhibitor (PAI)-1 (SERPINE1) SNPs With Myocardial Infarction, Plasma PAI-1, and Metabolic Parameters

The HIFMECH Study

P.E. Morange; N. Saut; M.C. Alessi; J.S. Yudkin; M. Margaglione; G. Di Minno; A. Hamsten; S.E. Humphries; D.A. Tregouet; I. Juhan-Vague

From INSERM, U626 (P.E.M., N.S., M.C.A., I.J.V.), Université de la Méditerranée, Marseille, France; the Diabetes and Cardiovascular Disease Academic Unit (J.S.Y.), Archway Campus, Royal Free and University College Medical School, London, UK; Instituto di Ricovero e Cura a Carattere Scientifico (M.M., G.D.M.), Ospedale Casa Sollievo della Sofferenza, San Giovani Rotondo, Italy; King Gustaf V Research Institute and Departments of Medicine and Cardiology (A.H.), Karolinska Hospital, Karolinska Institute, Stockholm, Sweden; the Center for Cardiovascular Genetics (S.E.H.), British Heart Foundation Laboratories, Rayne Building, Royal Free and University College Medical School, London, UK; and INSERM, UMR S 525 (D.A.T.), Université Pierre et Marie Curie-Paris6, UMR S 525, Paris, F-75634 France.

Correspondence to P.E. Morange, Lab. Hematology, CHU Timone. 264, Rue Saint-Pierre 13385 Marseille Cedex 05, France. E-mail pmorange{at}ap-hm.fr

Objective— The purpose of this study was to investigate the effects of plasminogen activator inhibitor-1 (PAI-1) gene (SERPINE1) single nucleotide polymorphisms (SNPs) on the risk of myocardial infarction (MI), on PAI-1 levels, and factors related to the metabolic syndrome.

Methods and Results— Eleven SNPs capturing the common genetic variation of the SERPINE1 gene were genotyped in the HIFMECH study. In the 510 male cases and their 543 age-matched controls, a significant gene-smoking interaction was observed. In nonsmokers, the rs7242-G allele was more frequent in cases than in controls (0.486 versus 0.382, P=0.013) whereas the haplotype derived from the rs2227631 (–844A>G)-G and rs2227683-A alleles was 3-fold lower in cases than in controls (0.042 versus 0.115, P=0.006). SERPINE1 haplotypes explained 3.5% (P=0.007) of the variability of PAI-1 levels, which was attributable to the combined effects of 3 SNPs, –844A>G, rs2227666, and rs2227694. The rs6092 (Ala15Thr) and rs7242 SNPs acted additively to explain 4.4% of the variability of plasma insulin levels and 1.6% of the variability of BMI (P<10^–3 and P=0.023, respectively).

Conclusions— SERPINE1 haplotypes are mildly associated with plasma levels of PAI-1 and with the risk of MI in nonsmokers. They are also associated with insulin levels and BMI.

HIFMECH is a European case-control study for myocardial infarction (MI). In the 510 male cases and their 543 age-matched controls, SERPINE1 haplotypes were mildly associated with plasma levels of PAI-1 and with the risk of MI in nonsmokers. They were also associated with insulin levels and BMI.

Key Words: metabolic syndrome • myocardial infarction • PAI-1 • SERPINE1

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