title: Common variants in the haemostatic gene pathway contribute to risk of early-onset myocardial infarction in the Italian population.
abstract: 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.
authors: Department of Biology and Genetics for Medical Sciences, University of Milan, Milano, Italy.
authors: Ilaria
authors: I
authors: Guella
authors: Stefano
authors: S
authors: Duga
authors: Diego
authors: D
authors: Ardissino
authors: Pier Angelica
authors: PA
authors: Merlini
authors: Flora
authors: F
authors: Peyvandi
authors: Pier Mannuccio
authors: PM
authors: Mannucci
authors: Rosanna
authors: R
authors: Asselta
mesh_terms: D000328:Adult; D017668:Age of Onset; D015703:Antigens, CD / Q000235:genetics*; D004252:DNA Mutational Analysis; D000074283:Endothelial Protein C Receptor; D005176:Factor XIII / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006487:Hemostasis / Q000235:genetics; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000453:epidemiology* / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D044382:Population Groups; D011956:Receptors, Cell Surface / Q000235:genetics*; D012306:Risk
chemical_list: D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011956:Receptors, Cell Surface; D005176:Factor XIII