Abstract
Genetic polymorphisms may be linked to inter-individual differences in erythropoietin (EPO) resistance. We investigated the -511C/T polymorphism of the IL-1B gene and the I/D polymorphism of the ACE gene for any association with EPO resistance index (ERI) in maintenance hemodialysis patients (n=167). Because EPO responsiveness is multi-factorial, we also included other possible influences (age, sex, time on dialysis, ACE inhibitor or angiotensin receptor blocker use, ferritin, transferrin saturation, intact PTH, high sensitivity C-reactive protein, albumin, Kt/V, and presence of diabetes mellitus) on ERI in our analyses. Multiple regression analysis showed significant association of the IL-1B-511CC and ACE DD polymorphisms with ERI (P=0.038 and P=0.004 in the recessive model, respectively). The combination (C) of alleles of two loci showed that C1 (I-T) was significantly associated with ERI in the co-dominant and recessive models (P=0.005 and P=0.0001, respectively). Subjects who did not carry C1 showed significantly decreased ERI (10.10+/-5.15 IU/kg weight/g hemoglobin) compared to other study subjects (C1/C1 and C1/-; 12.97+/-4.90 and 15.12+/-7.43 IU/kg weight/g hemoglobin, respectively). Our study indicates that the IL-1B-511C/T and ACE I/D polymorphisms may be useful genetic markers of EPO requirement in hemodialysis patients. These findings might also provide a new perspective on therapeutic approaches to the treatment of end stage renal disease patients with anemia.
Highlights
Since the introduction of recombinant human erythropoietin (EPO) in 1986, it has been an effective treatment for renal anemia in the majority of patients with end-stage renal disease (ESRD) (Winearls et al, 1986; Schaefer et al, 1989)
We evaluated the IL-1B-511C/T and angiotensin converting enzyme (ACE) I/D polymorphisms in patients in hemodialysis to determine the association between various polymorphisms and EPO resistance
Clinical data: The following clinical and laboratory data were obtained for three months prior to the time of the study, and average values were used for analysis: serum albumin, iron, total iron-binding capacity, ferritin, high sensitivity C-reactive protein, Kt/V, and intact parathyroid hormone (PTH) levels
Summary
Since the introduction of recombinant human erythropoietin (EPO) in 1986, it has been an effective treatment for renal anemia in the majority of patients with end-stage renal disease (ESRD) (Winearls et al, 1986; Schaefer et al, 1989). Mean angiotensin converting enzyme (ACE) levels in ACE DD carriers were approximately twice that found in ACE II genotype individuals (Rigat et al, 1990). Some investigators have observed an increase in EPO requirement in patients with the ACE II genotype undergoing continuous ambulatory peritoneal dialysis (CAPD) (Varagunam et al, 2003), but others have found no effect (Hatano et al, 2000). It seems possible, that polymorphisms of the IL-1B and ACE genes play a role in the development of EPO resistance in ESRD patients. Because EPO responsiveness is multi-factorial, we included other possible influences on EPO resistance in our analyses
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