Influencia genética en la mortalidad de pacientes diabéticos de tipo 2 en diálisis

Abstract

Introduction and aim: Diabetic nephropathy causes one-third of cases of end-stage renal disease in Spain. Several familial clustering studies have shown that genetic susceptibility may be involved in this pathologic process. Since renin-angiotensin system inhibitors have an important effect on this disease, it seems rational to study polymorphisms belonging to genes of this system such as angiotensin-converting enzyme 1 (ACE1) I/D, angiotensinogen (AGT) p.M235T, type 1 angiotensin II receptor (AGTR1) g.1166A>C and three polymorphisms of the type 2 angiotensin-converting enzyme (ACE2): rs4646124, rs2285666 and rs879922. The aim of this study was to evaluate the relationship between these polymorphisms and survival time of type II diabetic patients undergoing dialysis. Methods: We included 100 patients. We collected both the dates of entry in the dialysis program and death, along with other clinical features of interest. Individual genotypes were assigned by real-time polymerase chain reaction. Results: The survival curves for each polymorphism showed no significant differences between genotypes. However, multivariate Cox regression analysis, which allowed inclusion of other clinical variables, revealed statistically significant differences in the ACE1 (p = 0.013) and AGT (p = 0.015) polymorphisms. For each variant, we chose the allele that carried the highest mortality risk and created a new variable called "number of risk alleles". The relative risk of death was multiplied by 1.42 (95%:1.15-1.77 p = 0.0009) for each additional risk allele carried by the patient: D (ACE1), M (AGT), A (AGTR1) and G (ACE2, rs4646124). Similar results were obtained when the AGTR1 genotype was excluded (95% CI 1.46: 1.16-1.84 p = 0.0014). Conclusions: The combination of these allelic variants of the renin-angiotensin system genes plays a significant role in the mortality risk of type II diabetic patients on dialysis. © 2010 SEDYT.