Role of genetic polymorphisms in myocardial infarction at young age

Abstract

Acute myocardial infarction (AMI) in young adult presents a typical pattern of risk factors, clinical, angiographic and prognostic characteristics.In the last years we demonstrated that hemorheological profile is altered in these patients in a persistent way and independently of the number of risk factors and of the extent of coronary lesions. Thus, the hyperviscosity syndrome following AMI could be considered an intrinsic characteristic of these patients. Consequently it is possible to hypothesise the presence of a genetic background at the origin of this predisposition. If this background is able to influence the risk of ischemic heart disease, this should be particularly evident in young subjects.Since inflammatory mechanisms play a central role in mediating all phases of atherosclerosis, genes encoding for inflammatory or anti-inflammatory molecules are candidates for the risk of developing atherosclerosis.As atherosclerosis is the first cause of mortality in Western countries and if pro-inflammatory genotypes contribute to risk of coronary heart disease, alleles associated to disease susceptibility should not be included in the genetic background favouring longevity: People genetically predisposed to a weak inflammatory activity have fewer chances to develop cardiovascular disease and, therefore, have better chance for a long-life. According to this hypothesis, we studied in our population of young patients with AMI, the distribution of some polymorphisms influencing a inflammation and found an higher prevalence of pro-inflammatory polymorphisms (SNP A2080G of pyrin gene, SNP Gly670Arg of PECAM gene, C1019T of Cx 37 gene, SNP G1059C of PCR gene) and a lower prevalence of anti-inflammatory polymorphisms (Asp299Gly of TLR4 gene, SNP −1082 G/A of IL10 gene, CCR5 32).Results of these studies show that early myocardial infarction could be associated with a genetic predisposition to an intense inflammatory response, associated also to an hyperviscosity syndrome.

Genetics of longevity. Data from the studies on Sicilian centenarians

“…In particular, it has been demonstrated that centenarian offspring have an increased likelihood of surviving to 100 years and show a reduced prevalence of age associated diseases, such as CVD, and lower prevalence of CVD risk factors [1,30-32,50] Thus, genes involved in CVD may play an opposite role in human male longevity. Our data in male Sicilian population confirm this suggestion and emphasize the role of antagonistic pleiotropy in ageing and longevity [51,52]. A high frequency of proinflammatory CCR5wt variant, +896A TLR4 allele, -765 G Cox-2 allele, 1708A and 21 T 5-Lo alleles characterizes male Sicilian patients affected by MI (Table 3) [47-49].…”

Gap Junctions and Connexin Hemichannels Underpin Hemostasis and Thrombosis

“…19 Indeed, a single nucleotide polymorphism (C1019T) within the human Cx37 gene ( GJA4 ) has been reported to be a potential prognostic marker for atherosclerosis and myocardial infarction. 48,49 Given the established role of platelet-monocyte adhesion and the initiation or progression of atherosclerosis, it is tempting to speculate that the role of platelet connexin function may extend to platelet-immune cell intercellular signalling in a range of pathological conditions.…”

Prevalence of at-risk genotypes for genotoxic effects decreases with age in a randomly selected population in Flanders: a cross sectional study

“…For instance, in an ethnically homogeneous population, different age groups showed differences in the prevalence of certain polymorphisms in interleukin genes [32]. In particular, polymorphisms in genes related to inflammation, oxidative stress [32-34] and mitochondrial DNA [35] were found to be associated with differences in longevity. Although there are some contradictory reports in the literature [36,37] and although paradoxical effects were reported [18], a series of observations indicate that genetic traits in phase II enzymes, expected on mechanistic terms to increase risk, are indeed associated in humans with an increase in risk of cancer [19,38-43] or coronary heart disease [44,45].…”