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Thromb Haemost 2011; 106(04): 855-864
DOI: 10.1160/TH11-04-0247
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

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

Ilaria Guella
1   Dipartimento di Biologia e Genetica per le Scienze Mediche, Università degli Studi di Milano, Milano, Italy
,
Stefano Duga
1   Dipartimento di Biologia e Genetica per le Scienze Mediche, Università degli Studi di Milano, Milano, Italy
,
Diego Ardissino
2   Unità Operativa di Cardiologia, Dipartimento Cardio-Polmonare, Azienda Ospedaliero-Universitaria di Parma, Parma, Italy
,
Pier Angelica Merlini
3   Dipartimento di Cardiologia, Ospedale Niguarda, Milano, Italy
,
Flora Peyvandi
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
,
Pier Mannuccio Mannucci
5   Scientific Direction, IRCCS Fondazione Cà Granda Ospedale Maggiore, Milan, Italy
,
Rosanna Asselta
1   Dipartimento di Biologia e Genetica per le Scienze Mediche, Università degli Studi di Milano, Milano, Italy
› Author Affiliations Financial support: This study was supported by “Progetto a concorso” for years 2009/2010 from “IRCCS Fondazione Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena” to RA.
Further Information

Publication History

Received: 18 April 2011

Accepted after major revision: 18 July 2011

Publication Date:
29 November 2017 (online)

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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.

Keywords

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

 

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