Relação entre os polimorfismos rs1801133 e rs1801131 da metilenotetrahidrofolato redutase e parâmetros estruturais e funcionais do coração em pacientes com retinopatia diabética

Abstract

Diabetes Mellitus is a disease caused by a deficiency in the release or use of the hormone insulin, leading to a state of hyperglycemia. Diabetic retinopathy, a microvascular complication of diabetes mellitus, may increase the risk of cardiovascular events in diabetic patients. Cardiovascular diseases are still the major cause of death worldwide. The enzyme Metilotetrahydrofolate reductase, responsible for the release of the active form of folate in the body, may have its efficiency affected by dietary and genetic factors, such as the polymorphisms rs1801133 and 1801131, and deficiency of vitamin B12, which is a cofactor of the metabolism of this enzyme. The reduction in MTHFR activity can lead to an increase in plasma homocysteine, which in turn is related to insulin resistance and some chronic complications of diabetes, such as retinopathy. Studies have shown that hyperhomocysteinemia is able to increase the risk of cardiovascular disease and cause an increase in the diameter of the left atrium. The aim of this study was to verify the relationship of rs1801133 and 1801131 polymorphisms with structural and functional parameters of the heart of patients with diabetic retinopathy. It also aimed to analyze the genotypes of patients with RD regarding the polymorphisms, and to verify biochemical, nutritional, anthropometric and lifestyle parameters of the participants involved in the specific genotyped groups. This study is a cross-sectional study with an epidemiological basis, from a larger study entitled "Epigenetics + genetics: identification of markers for Diabetic Retinopathy". This study had 65 patients diagnosed with diabetic retinopathy, with a mean age of 62.46 ± 8,421. 42 participants had non-proliferative diabetic retinopathy and 23 proliferative diabetic retinopathy. The genotypes of rs1801133 and rs1801131 were determined using the PCR-RFLP technique. Participants were categorized according to biochemical, cardiological (from echocardiogram and eletrocardiograma exam), anthropometric, genetic, lifestyle and vitamin B9 and B12 consumption variables. Fischer's exact test and Poisson regression were performed to assess the relationship between variables. The only significant association found in Fischer's exact test was between increasing the left atrium diameter and the rs1801133, although no association was found with rs1801131. There was no significant association between the diameter of the left atrium and biochemical, anthropometric, food consumption, and lifestyle variables. All study participants had insufficient consumption of at least one of the two micronutrients. The regression model showed that the increase in the left atrium was associated with the T allele, with a prevalence ratio of 0.912. The regression model also showed an association between the increase in left atrium diameter with ejection fraction, final stroke volume and heart rate. The main result of this study suggest an association between the T allele and the increase in diameter of the left atrium. In addition to the association with polymorphism, in the regression model there was also an association between left atrium diameter and ejection fraction, final stroke volume and heart rate.