The impact of gene polymorphisms in angiotensin receptor 1 and aldosterone synthase in peritoneal dialysis patients.

Abstract

Longevity of peritoneal membrane is an important issue in patients treated with peritoneal dialysis (PD). In our study, we studied the impact of angiotensin receptor 1 (AGT R1) and aldosterone synthase (CYP11B2) gene polymorphism on peritoneal concentrations of interleukin-6 (PI-IL-6), vascular endothelial growth factor (PI-VEGF), plasminogen activator inhibitor-1 (PI-PAI-1), transforming growth factor-β (PI-TGF-β), and cancer antigen-125 (PI-CA-125) as known markers of peritoneal fibrosis. The single nucleotide polymorphism rs5186 (A1166C) in AGT R1 gene is located in 3' untranslated region (UTR) of the gene, while polymorphism rs1799998 (T -344 C) in CYP11B2 gene is located in the promoter region of the gene. We compared marker concentrations in patients with genotype DD vs. Dd and dd for AGT R1 and patients with genotype HH vs. Hh and hh for CYP11B2. The results show that polymorphism of CYP11B2 gene is associated with serum concentration of aldosterone. Patients with genotype HH had statistically significantly lower serum concentration of aldosterone (p=0.04). These patients also showed a trend to a lower rate of production of I-IL-6 (p=0.07), which correlated with lower concentrations of PAI-1 (p=0.002) and VEGF (p=0.005). AGT R1 gene polymorphism did not show any association with studied variables. Our findings suggest the possibility of genetic predisposition for development of peritoneal fibrosis that could be important for identification of patients with an "unfavorable" genotype, which could lead to customized prescription of appropriate therapy and personalized patient management. .