Polimorfismo do gene da óxio nítrico sintase endotelial (glu298asp) e da adiponectina (adipoq +45 t>G) como potenciais marcadores de hipertensão e inflamação em uma população afrodescendente

Abstract

The Brazilian black population corresponds to 54.9% of the country's population, however, still has greater social and economic vulnerability, resulting in greater susceptibility to health damage and health. One of the most prevalent diseases in the black population is hypertension, which, along with cardiovascular disease, stands out as the leading cause of death and hospitalization in Brazil. Although mortalit from cardiovascular disease has declined in recent years overall, in black and low- income individuals this situation remains unchanged. Because of this, the search for genetic markers in this specific population becomes relevant. Variations in the gene that secretes nitric oxide in blood vessels have been reported to be important for vasodilation and blood pressure control, as well changes in the adiponectin gene, an cytokine involved in the regulation of lipid and glycemic metabolism, however, the importance of these variations and their role in the development and progression of chronic diseases in the black population is not yet known. The aim of this study was to evaluate the effect of two polymorphisms on different genes and their association with hypertensive disease and inflammation in blacks. The study included 203 self- declared black individuals, mostly women, whose prevalence of hypertension wa 53.8%, among which 41% of hypertensive patients presented with controlled disease, 51% uncontrolled blood pressure, and 8% were classified as resistant hypertension, a rarer phenotype of the disease that does not respond with decreased blood pressure despite the use of 3 antihypertensive drugs of different classes including a diuretic. Regarding the polymorphisms evaluated, the presence of two mutated alleles in either one and obesity increased the odds ratio for uncontrolled hypertension. The mutated allele in ADIPOQ+45T>G polymorphism was associated with smoking in the uncontrolled hypertension group, and with significantly lower

adiponectin levels, considered to be an important anti-inflammatory and anti- atherosclerotic cytokine, especially in the uncontrolled group. In vitro evaluation, cell of different genotypes of the Glu298Asp polymorphism showed differences in the inflammatory response evaluated by levels of pro and anti-inflammatory cytokines and also expression of inflammatory genes. The G allele showed a protective role and the T allele was more susceptible to inflammation. The results of this work indicate that the Glu298Asp polymorphism of the endothelial nitric oxide synthase gene can be used as a biomarker of cardiovascular changes in the black population.