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Common variants in the haemostatic gene pathway contribute to risk of early-onset myocardial infarction in the Italian population

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: https://doi.org/10.1160/TH11-04-0247
Issue: 2011: 106/4 (Oct) pp. 567–752
Pages: 655-664

Common variants in the haemostatic gene pathway contribute to risk of early-onset myocardial infarction in the Italian population

Online Supplementary Material

I. Guella (1), S. Duga (1), D. Ardissino (2), P. A. Merlini (3), F. Peyvandi (4), P. M. Mannucci (5), R. Asselta (1)

(1) Dipartimento di Biologia e Genetica per le Scienze Mediche, Università degli Studi di Milano, Milano, Italy; (2) Unità Operativa di Cardiologia, Dipartimento Cardio-Polmonare, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy; (3) Dipartimento di Cardiologia, Ospedale Niguarda, Milano, Italy; (4) Centro Emofilia e Trombosi A. Bianchi Bonomi, Dipartimento di Medicina e Specialità Mediche, IRCCS Fondazione Cà Granda Ospedale Maggiore, Università degli Studi di Milano, Milano, Italy; (5) Scientific Direction, IRCCS Fondazione Cà Granda Ospedale Maggiore, Milan, Italy

Keywords

Association study, common genetic variants, early-onset myocardial infarction, genetic risk score, haemostatic gene pathway.

Summary

Occlusive coronary thrombus formation superimposed on an atherosclerotic plaque is the ultimate event leading to myocardial infarction (MI). Therefore, haemostatic proteins may represent important players in the pathogenesis of MI. It was the objective of this study to evaluate, in a comprehensive way, the role of haemostatic gene polymorphisms in predisposition to premature MI. A total of 810 single nucleotide polymorphisms (SNPs) in 37 genes were assessed for association with MI in a large cohort (1,670 males, 210 females) of Italian patients who suffered from an MI event before the age of 45, and an equal number of controls. Thirty-eight SNPs selected from the literature were genotyped using the SNPlex technology, whereas genotypes for the remaining 772 SNPs were extracted from a previous genome-wide association study. Genotypes were analysed by a standard case-control analysis corrected for classical cardiovascular risk factors, and by haplotype analysis. A weighted Genetic Risk Score (GRS) was calculated. Evidence for association with MI after covariate correction was found for 35 SNPs in 12 loci: F5, PROS1, F11, ITGA2, F12, F13A1, SERPINE1, PLAT, VWF, THBD, PROCR, and F9. The weighted GRS was constructed by including the top SNP for each of the 12 associated loci. The GRS distribution was significantly different between cases and controls, and subjects in the highest quintile had a 2.69-fold increased risk for MI compared with those in the lowest quintile. Our results suggest that a GRS, based on the combined effect of several risk alleles in different haemostatic genes, is associated with an increased risk of MI.

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