ALOX5, LPA, MMP9 and TPO gene polymorphisms increase atherothrombosis susceptibility in middle-aged Mexicans

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.

Keywords: Native Americans; cardiovascular diseases; gene polymorphisms; multiloci studies; myocardial infarction; stroke.

Figure 1.

Multidimensional scale plot of genetic distances (R_st) values estimated from (a) all polymorphisms explored and (b) only with the four susceptibility polymorphisms. CMA, clinical manifestations of atherothrombosis; GC, genomic control; HG, healthy group.