Studies of Gene Polymorphisms and Myocardial Infarction. An Endangered Species?

Abstract

See article on page S 365-72 Clinical studies show that almost 10% of acute coronary events occur in patients under 45 years of age and it has been estimated that genetic factors contribute to between 20% and 60% of these events. 1 In young individuals with acute myocardial infarction (AMI), 2 an apparent reduction in plasma fibrinolytic activity could play a causal role in acute coronary events. High plasma concentrations of plasminogen activator inhibitor tipe 1 (PAI-1) are associated with thrombotic events. 3 An association between the 4G/5G polymorphism in the PAI-1 gene and ST elevation acute myocardial infarction (STEMI) has been described in young patients. This polymorphism consists of the insertion/deletion of a guanine base in the promoting region in position –675, resulting in the presence of the 4G or 5G allele; the polymorphism exerts a regulatory action on the plasma concentration of PAI-1. 4,5 The frequency with which the 4G/5G polymorphism presents varies in different parts of the world leading to variations in PAI plasma concentrations across populations. The increased concentration of PAI-1 in plasma is associated with increased mortality and AMI in subjects under 45 years of age. Individuals homozygous for the 4G allele (4G/4G) are also reported to have PAI-1 concentrations which are higher than those in subjects who are homozygous for the 5G allele (5G/5G). 6 We would therefore expect individuals who are homozygous for the 4G/4G allele to have increased thrombogenic activity and a subsequent higher incidence of AMI. However, previous studies that have investigated this association have provided contradictory results. In this issue of the Revista Espanola de Cardiologia, Isordia-Salas et al 7 present the results of an interesting study assessing the relationship between the 4G/5G polymorphism in the PAI-1 gene in young patients (age ≤45 years) with STEMI and the possible influence of the polymorphism in regulating PAI-1 plasma levels. The researchers consecutively recruited 127 patients aged ≤45 years with STEMI admitted to the Intensive Cardiovascular Care Unit of the Cardiology Hospital in the Centro Medico Nacional Siglo XXI (Mexico) between January 2006 and March 2007. They also recruited 127 blood donors, who were assumed to be free of cardiovascular risk factors, as a control group. Determination of PAI-1 plasma levels were performed in blood samples taken 6 weeks after STEMI using an immunoenzymatic technique (ELISA) (Coaliza PAI-1, Chromogenix, Milan, Italy). Genotype determination was performed on DNA obtained from leukocyte concentrate using polymerase chain reaction techniques. The study’s most important findings were that: – The most common genotype in patients with STEMI was 4G/5G, with the 4G/4G genotype being found in only 7% of cases. No statistically significant differences in allelic frequency were observed between the control group and patients with AMI – The multivariate logistic regression analysis for AMI risk showed that the presence of the 4G allele was associated with increased risk for myocardial infarction (odds ratio [OR] =2.29), but that the risk was lower than that associated with conventional cardiovascular risk factors such as smoking, high blood pressure, and a family history of heart disease. The risk associated with smoking was >15 times greater than that associated with the polymorphism. From a clinical point of view, then, the polymorphism’s contribution to cardiovascular risk was small in comparison with more established risk factors; further research is required to better define