Genetic variants of the endothelial nitric oxide synthase and renal function in Polycystic Kidney Disease

Abstract

Autosomal dominant polycystic kidney disease (ADPKD), characterized by the appearance of renal cysts from any portion of the nephron, is caused by two types of mutations, including PKD1 and PKD2 genes, having primarily as extra-renal manifestation hypertension and aneurysm. In this context, genetic risk factors play an important role in the progression of the disease, with emphasis on genes involved in the integrity of the arterial wall, like the nitric oxide synthase endothelial (eNOS), important for regulating vasodilator tone and the control of blood pressure in humans. This study aims to evaluate the distribution of the polymorphism eNOS-G894T (rs 1799983) in patients with a diagnosis of ADPKD and their relatives in the first degree; evaluate the relationship between renal function and the polymorphism in patients with ADPKD, and analyze the odds ratio for ADPKD, with respect to clinical and genetic factors. Will be studied 240 individuals, regardless of sex, ethnicity, or age, divided into six groups: G1-20 individuals diagnosed with familial polycystic kidney; G2-20 first-degree relatives of G1, without a diagnosis of disease; G3-50 individuals with a diagnosis of the sporadic polycystic kidney; G4-50 families in the first degree of G3; G5-50 individuals with negative results for the studies of disease; G6-50 families in the first degree of G5. The individuals will be subject to collection of peripheral blood for DNA extraction, followed by amplification of the polymorphic fragment by polymerase chain reaction (PCR). The renal function is evaluated by serum creatinine and urea dosing. The test will include statistical analysis, Tukey Fisher's exact test or Chi-square (for Hardy-Weinberg), multivariate regression, t-test and with a significance level of P<0.05.(AU)