Clinical Significance of IL-6 Gene Polymorphism on Erythropoietin Responsiveness in Hemodialysis Patients

Abstract Background The plasma levels of the cytokine interleukin-6 (IL-6) have been reported to be associated with risk of chronic kidney disease (CKD) and erythropoietin (EPO) responsiveness. The G/C promoter polymorphism of IL-6 is associated with expression and levels of IL-6, so it may confer increased risk to CKD and modulate EPO responsiveness. Aim of the Work This study aims to evaluate the frequency of 174G/C IL-6 gene promoter polymorphism in hemodialysis (HD) patients and to assess the impact of this allelic variation on erythropoietin (EPO) responsiveness. Patients and Methods This study was conducted on fifty Chronic Kidney Disease (CKD) patients undergoing hemodialysis (HD) recruited from Nephrology Medicine Department at Ain Shams University hospitals, and ten healthy age and sex matched controls. All patients received recombinant human erythropoeitin (rHu-Epo) regimens for treatment of anemia. All the patients were subjected to full history taking, basic laboratory investigations (CBC, Iron profile and kidney function tests) as well as determination of IL-6 rs1800795 (-174 G/C) gene polymorphism using Real time-polymerase chain reaction technique (RT-PCR). The patient’s group was further classified into two subgroups according to Hb level in response to erythropoietin stimulating agents (ESAs) in accordance with the European Best Practice Guidelines, in which responders have a Hb level ≥11 g/dl, and ESA non-responders have a Hb level<11 g/dl. The Erythropoietin resistance index (ERI) was calculated for all patients, with a median (IQR) of 16.5 (14.31 - 19.96). Accordingly all patients were further classified into tertiles according to the ERI. The higher tertile group is classified as more hypo-responsive/resistant. Results In the present study, The IL-6 -174 G/G genotype was the most common among the cases group. Seventy four percent of the patients had the wild GG genotype and 24% had heterozygous GC genotype while only 2% had the homozygous CC genotype. In the control group the G/G genotype was detected in (80%) of subjects followed by G/C genotype (20%). No statistically significant difference was observed between the control and cases group regarding the IL-6 genotype frequencies. Only eight out of fifty (16%) patients reached the target Hb, 4 of them (50%) had the GG genotype and the other 4 (50%) had the GC genotype. The non-responders genotypes were distributed as 78.6% GG genotype, 19% GC genotype and 2.4% with CC genotype. There was no statistical significant difference regarding the genotype frequencies of IL-6 gene polymorphism between the two groups. Similarly no statistically significant association was found between the IL-6 gene genotypes and the ERI tertiles. Conclusion IL-6 -174 G/C gene polymorphism was not found to be associated with EPO hypo-responsiveness in CKD patients in the studied group nor with the increased Erythropoeitin resistance index (ERI) values among them.