Presença de polimorfismos genéticos da paraoxonase humana-1 e alterações metabólicas em jovens com doença coronariana aterosclerótica

Abstract

Atherosclerotic coronary artery disease (CAD) is the leading cause of death worldwide and has been occurring in the last decade in increasingly younger age groups. Many of these individuals do not have the risk factors classically known from the Framingham Study for the development of the disease. Since CAD is a complex disease, with a multifactorial etiology, it is understood that in its evolution there is a little-known interaction of environmental factors acting on an individual with genetic characteristics predisposing to the early occurrence of the disease. As the most common abnormality observed in this population is the low levels of high density lipoprotein (HDL-col), it was decided to study its genetic modulators, specifically human Paraoxonase 1. This enzyme was chosen because it is present in large quantities in the particles of HDL-col and to whom the anti-atherogenic properties are attributed with a consequent impact on the reduction of cardiovascular risk. Objectives: to evaluate the associations of the polymorphisms of the Paraoxonase1 (PON1) genes C108T and L55M with the classic risk factors for premature atherosclerotic coronary disease. Methodology: cross-sectional, case-control study, carried out from January 2016 to January 2019. 113 individuals were evaluated, of which 81 were diagnosed with CAD and 32 were healthy, men under 45 years old and women under 55 years. Results: the most frequent biochemical variables in the cases were dyslipidemia, characterized by high levels of total cholesterol, LDL-col and HDL- col, as well as fasting blood glucose and glycated hemoglobin. Regarding the clinical characteristics, high levels of AC and BMI were significantly observed. In the genotypic evaluation, those with the T allele of the C108T gene had a significant association with dyslipidemia (p <0.042) and those with the M allele of the L55M gene had significantly higher BMI values (p <0.011). The linkage imbalance of the C108T and L55M haplotypes was significantly associated with the risk of coronary disease (p <0.013). The MM genotype was significantly associated with the involvement of the coronary territory of the circumflex artery (Cx) (p <0.038). The TT genotype was associated with higher levels of TSH in CAD cases (p <0.021). No significant associations were found between genotypes and other risk factors for CAD in cases and controls. Conclusion: The presence of PON 1 polymorphisms C108T and L55M, alone, does not produce a significant increase in the occurrence of atherosclerotic coronary disease in young people, however the elevation of total cholesterol levels and low HDL levels produce a risk greater than 3 (p <0.033) and 9 times (p <0.021) respectively in the chance of premature CAD, with the prevalence of these risk factors under possible genetic modulation.