Influência do polimorfismo no sítio PvuII do gene LPL em indivíduos com diabetes mellitus tipo 2

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic disease characterized by insulin resistance and the pancreas's inability to produce enough insulin to control blood glucose levels. In Brazil, T2DM is a growing public health problem, and the main risk factors for the development of the disease include obesity, hypertension, physical inactivity, poor diet, and an aging population. Genetic predisposition to these risk factors has been widely studied. The LPL gene, which encodes lipoprotein lipase that acts in lipid metabolism, particularly in the hydrolysis of triglycerides into chylomicrons and very low-density lipoprotein (VLDL), has polymorphisms that may affect the enzyme's activity. In this study, we focused on the PvuII polymorphism (rs285) caused by the transition of base CT in the 6th intron of the LPL gene. Although it does not directly alter the enzyme's structure, it can affect the overall hydrolysis of TG by altering expression and gene regulation through linkage imbalance, modifying regulatory factor binding sites, precursor mRNA splicing efficiency, and LPL expression levels. With that, the objective of this study was to evaluate the association of the PvuII polymorphism of the LPL gene with anthropometric parameters, lipid profile, and blood pressure in individuals with type 2 diabetes (DM2). This was an analytical, multicenter study with a cross-sectional design. Socioeconomic, clinical, nutritional, and biochemical data from individuals with DM2 from the cities of Governador Valadares (MG), Viçosa (MG), São Paulo (SP), and Porto Alegre (RS) were used. All participants who read and signed the informed consent form (ICF) underwent consultations and blood sample collections for the performance of biochemical and molecular tests. The PvuII LPL polymorphism was identified through polymerase chain reaction combined with restriction fragment length polymorphism (PCR-RFLP). Subsequently, the Pearson chi-square test was performed to associate this polymorphism with anthropometric parameters, glycemic and lipid profiles, obesity, and hypertension. It was observed that elevated body mass index (BMI), waist circunference (WC), and waist-to-height ratio (WHtR) are directly linked and corroborate with an increased risk of cardiovascular diseases. The study of the polymorphism showed the prevalence of the genotype CT in mixed-race individuals and TT in black individuals. Those with the TT genotype showed a greater predisposition to low levels of high-density lipoprotein cholesterol (HDL-c), which supports the risk of cardiovascular complications. However, there was a noted need for social and public health interventions, as, regardless of sex, individuals exhibited lipid and glycemic profiles indicating inadequate management of type 2 diabetes mellitus (DM2) and a risk of cardiovascular complications.