Análise molecular do polimorfismo do gene CYP3A5 em pacientes com aterosclerose

Abstract

Cardiovascular diseases are ranked as one of the diseases that most kill the Brazilian population and of other countries as well, one of them, being atherosclerosis. It is a chronic inflammatory disease that occurs by the accumulation of lipids in the inner layer of the arteries. There are numerous risk factors for the genesis of this disease, divided into modifiable ones such as hypertension, smoking, high levels of low density cholesterol, sedentary lifestyle and others. Non-modifiable ones are: genetic factors, premature family history for heart disease, sex, age and others. About 400 genes may be involved in this pathology, both mutations, deletions and / or polymorphisms are implicated in atherosclerosis, related to regulation of endothelial function, coagulation, inflammation and lipid metabolism. Genetic association with atherosclerosis is increasingly expanding, being the object of studies, mainly with polymorphisms of the cytochrome P450 genes. The CYP3A5 gene encodes monooxygenase proteins that are part of drug metabolism, cholesterol synthesis, steroids, and other lipids; (A6986G), produces a truncated / inactive protein due to a splicing error, and there may be a relation of the polymorphism altering the enzymatic/protein activity contributing to the development of atherosclerosis. This study aimed to analyze the CYP3A5*3 gene polymorphism in the groups of individuals with the diagnosis of atherosclerosis and in the control group. Peripheral blood samples were collected from 200 patients with a diagnosis of atherosclerotic disease based on clinical exams and confirmed with imaging exams and 100 patients for the control group, without atherosclerotic disease. A significant difference was observed in both groups (case vs. control) in relation to the CYP3A5*3 gene polymorphism, where the highest frequency of the genotype was CYP3A5*1/*3 (p= 0.0394). The mutant homozygous genotype (CYP3A5*3/*3) was 6 times higher in patients with atherosclerosis than in the control group, and was also statistically significant. According to the male gender group, a 6,5-fold risk of CYP3A5*3/*3 genotype was observed in patients with atherosclerosis (p= 0.0185), already in relation to females, a relation (p= 0.5928). Observing hypertensive patients, there was also no relation between them and atherosclerosis (p= 0.9240). Our population showed a heterozygosity in relation to other populations, mainly in relation to the mutant homozygous genotype. In most cardiovascular diseases, it affects men, and can be explained by the hormonal factor, in which the CYP3A5 gene is involved not only in lipid metabolism but also in hormonal synthesis, especially testosterone, where men with the CYP3A5*3/*3 are 6,5 times more likely to develop atherosclerosis, different from the female sex. There was no association of the mutant homozygous genotype in atherosclerotic patients with arterial hypertension, even though it was a major risk factor for cardiovascular disease. In view of this, the studied population is heterozygous, being a characteristic of this population studied and that the CYP3A5*3/*3 genotype identifies a strong association with atherosclerosis in men.