T helper cell‑related cytokine gene polymorphisms and vitamin D pathway gene polymorphisms as predictors of survival probability in patients on renal replacement therapy

INTRODUCTION Negative outcomes in patients on renal replacement therapy (RRT) may have a source in T helper (Th)-cell imbalance or vitamin D deficiency.

OBJECTIVES We examined the association of genes encoding cytokines related to Th1 and Th2 cells and vitamin D pathway genes with survival probability of patients on RRT.

PATIENTS AND METHODS The study included 1253 patients on hemodialysis. IL13, IL4R, IL18, IL12A, IL12B, IL28B, MCP1, GC, VDR, and RXRA gene polymorphisms were tested. The Kaplan–Meier method with the log‑rank test was used to estimate significance of survival probabilities.

RESULTS Patients carrying the IL13 minor T allele had an increased risk of death compared with CC subjects (log‑rank test, P = 0.005; hazard ratio [HR], 1.40; 95% confidence interval [CI], 1.11–1.76; P = 0.005). IL28B rs8099 917 GG patients had higher mortality rates compared with IL28B GT+TT carriers (log‑rank test, P = 0.04; HR, 1.82; 95% CI, 1.10–3.01; P =0.02). IL28B rs12979860 TT carriers had an increased risk of death compared with CC+CT carriers (log‑rank test, P = 0.02; HR, 1.62; 95% CI, 1.09–2.42; P = 0.02) only when they were negative for hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. The prevalence of coronary artery disease differed significantly among patients with the IL28B rs12979860 TT genotype compared with CC+CT carriers (odds ratio, 1.87; 95% CI, 1.14–3.09; P = 0.01). There was no association between the GC, VDR, and RXRA nucleotide variants and survival.

CONCLUSIONS The IL13 rs20541 T allele and IL28B rs8099917 GG genotype are negative predictors of survival in patients on RRT, while the IL28B rs12979860 TT genotype increases the risk of death only in patients negative for HBV or HCV infection.