Abstract
Atherothrombosis is the cornerstone of cardiovascular diseases and the primary cause of death worldwide. Genetic contribution to disturbances in lipid metabolism, coagulation, inflammation and oxidative stress increase the susceptibility to its development and progression. Given its multifactorial nature, the multiloci studies have been proposed as potential predictors of susceptibility. A cross-sectional study was conducted to explore the contribution of nine genes involved in oxidative stress, inflammatory and thrombotic processes in 204 subjects with atherothrombosis matched by age and gender with a healthy group (n = 204). To evaluate the possibility of spurious associations owing to the Mexican population genetic heterogeneity as well as its ancestral origins, 300 unrelated mestizo individuals and 329 Native Americans were also included. ALOX5, LPA, MMP9 and TPO gene polymorphisms, as well as their multiallelic combinations, were twice to four times more frequent in those individuals with clinical manifestations of atherothrombosis than in the healthy group. Once adjusting for population stratification was done, these differences remained. Our results add further evidence on the contribution of ALOX5, LPA, MMP9 and TPO polymorphisms to atherothrombosis development in the middle-aged group, emphasizing the multiethnic studies in search of gene risk polymorphisms.
Highlights
Cardiovascular diseases (CVDs) are the leading cause of global death; low- and middle-income countries are where more than three-quarters of the deceases occur [1,2]
The clinical manifestations of atherothrombosis (CMA) group had the biggest share of individuals smoking or having smoked more than two cigarette packs per year ( p = 0.004)
In the present cross-sectional study, the polymorphisms of nine genes involved in inflammation, coagulation disorders and oxidative stress were evaluated in a group with CMA matched with a healthy group
Summary
Cardiovascular diseases (CVDs) are the leading cause of global death; low- and middle-income countries are where more than three-quarters of the deceases occur [1,2]. Atherothrombosis, a clinical manifestation of atherosclerosis related to arterial occlusive thrombosis, is the essence of these two medical conditions [1,4] Lifestyle behaviours such as tobacco and alcohol dependence, diet and reduced physical activity have been associated with an increased atherothrombosis risk [1,4]. The eNOS dinucleotide polymorphism, (CA)n, has been positively associated with coronary artery disease risk; the number of repeats seems to modulate the splicing efficiency, controlling the gene expression and enzymatic activity [14]. The large repeat alleles, (GT), of the promoter region of HMOX1, have been linked to low enzyme activity and an increase in coronary artery disease and myocardial infarction risks [15,16,17]. Candidate genes related to endothelial dysfunction, such as nicotinamide adenine dinucleotide phosphate oxidases (NOX), and NOX4, have been proposed, this matter has been hardly studied [18,19]
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