Níveis de metilação dos genes LPL, ADRB3 E MTHFR, status inflamatório, antropométrico e alimentar em indivíduos com estimativas de LDL-C calculadas a partir de duas equações

Abstract

The concentration of low-density lipoprotein cholesterol has been considered as a major modifiable risk factor for cardiovascular disease and may be influenced by nutritional status and changes in the methylation profile of genes that are involved in lipid metabolism, among other factors . However, there are difficulties in obtaining the concentrations of this lipoprotein, since the direct methods are costly, with the Friedewald and Martin equations being used to estimate their concentrations. In this sense, the objective of the present study was to estimate and compare the concentrations of low density lipoprotein estimated by the Friedewald and Martin equations and to explore the occurrence of association with the methylation levels of the LPL, ADRB3 and MTHFR genes, inflammatory, anthropometric status and food consumption. This is a cross-sectional, population-based study involving 236 adults of both sexes (37.5 years), from the east and west areas of the municipality of João Pessoa. Data collection was performed through home visits, after conducting a pilot study, where questionnaires were applied on socioeconomic, demographic, epidemiological characterization, lifestyle, food consumption and anthropometric status. Serum concentrations of total antioxidant capacity, alpha-1-acid glycoprotein, C-reactive protein, malondealdehyde, lipid profile, folic acid, cobalamin and homocysteine were analyzed. Analyzes of DNA methylation levels in the promoters of the LPL, MTHFR, ADRB3 genes were performed by the High Resolution Melting method. There were differences between the low density lipoprotein concentrations in relation to the two calculation estimates, these values being underestimated (10.57 mg / dL), when calculated by the Friedewald equation. It was observed that malondealdehyde influenced the increase of the low density lipoprotein concentrations estimated according to the two equations in all the linear regression models, with coefficients between 6.25 and 10.29 nmol / L and p-value between 0.000 and 0.020. DNA methylation levels decreased in the ADRB3 gene and increased DNA methylation levels in the MTHFR gene (p <0.05) when low density lipoprotein was calculated by the Martin equation (≥ 70 mg / dL). It was verified The direct influence of cholesterol and homocysteine consumption on lowdensity lipoprotein concentrations, according to Friedewald. We also found a positive relationship between waist circumference and age with low density lipoprotein concentrations, involving the methylation levels of the three genes. It is concluded that the variable that most influenced the increase of low density lipoprotein in all models was malondealdehyde, the largest increase being observed in the model involving the MTHFR gene, according to Friedewald. The methylation levels of the ADRB3 and MTHFR genes were different according to Martin's equation, using lower cut-off concentrations of low-density lipoprotein. This study is unprecedented and may help in the estimation of the calculation of low density lipoprotein in clinical practice in populations; as well as to target intervention strategies in relation to the variables that influence the increase of low density lipoprotein concentrations.