Estudo de associação entre frequência genotípica e alélica dos polimorfismos dos genes LEP, LEPR, TNF-α, PLA2G7 com índice de massa corpórea (IMC) de pacientes com aterosclerose subclínica

Abstract

Obesity is a clinical condition characterized by the excessive accumulation of body fat with multifactorial causes that reaches epidemic proportions throughout the world. It isthe main contributor to mortality from cardiovascular disease (CVD), and is strongly associated with the prognosis of atherosclerosis, a hallmark of coronary artery disease (CAD). In this disease, there is an imbalance of adipokines with a significant increase in pro-inflammatory cytokines, which trigger a chronic inflammatory state. The genetic component is a significant factor and a risk determinant for the pathophysiology of obesity. Evidence shows that the presence of single nucleotide polymorphisms (SNPs) in the genes of some adipokines can alter their serum concentrations and predispose to obesity. The present work investigated the association between the genes and polymorphisms of leptin (rs2383206 A/G), leptin receptor (rs10757274 A/G) and (rs10757278 A/G), TNF-a (rs1799724 C/T), and PLA2G7 (rs1051931 C/T) and (rs76863441 G/T) with body mass index of patients with subclinical atherosclerosis (SA). 325 patients of both genders were recruited from the Instituto Dante Pazzanese de Cardiologia (DPCI). Sample stratification was based on body mass index (BMI), data presented as mean ± standard deviation, dividing the group into eutrophic, overweight and obese. The QIAamp DNA Blood Mini Kit was used to perform DNA isolation. Genotyping was performed by Rotor-Gene Q Real-Time PCR Detection System. And the statistical analysis was performed with the SPSS® 22.0 program with significance established at p<0.05. All individuals were evaluated for anthropometric and laboratory characteristics, clinical evaluation and genetic polymorphism. The results revealed that of the 325 patients with AS, 128 were obese patients (BMI: 33.95±3.38); 137 were overweight or pre-obese (BMI: 27.42±1.34) and 60 were normal or eutrophic (BMI: 22.86±1.7). Among the patients included, there was a higher percentage of females in the eutrophic group 60%, overweight 65 and obese 59.4%. And the average age between the groups was 59 years.. The TT genotype of the rs1799724 polymorphism was significantly more frequent in the group of obese people 91.2% (114) (p: <0.001). The G allele of (rs76863441) was identified in 100% of the groups analyzed (p: 0.03). The T allele of SNP rs1051931 and the G allele (rs2383206) were more prevalent in patients in the obese group, 44.4% (56) and 80.2% (101) respectively. The dominant genotype GG+ AG of the polymorphism (rs10757278) was more frequent in eutrophic patients 81% (47), (P: 0.008). Similar to rs10757274, a higher frequency of the dominant genotype GG +AG was observed in eutrophic patients, 86.2% (50). Obesity and inflammation usually manifest together, being intrinsically related to the development of cardiovascular diseases, such as subclinical atherosclerosis. And the presence of polymorphisms in the genes of leptin, leptin receptor (LEPR), TNF-α and (PLA2) can alter the serum concentrations of adipokines and predispose to obesity.