Polymorphisms in two genes, IL-1B and ACE, are associated with erythropoietin resistance in Korean patients on maintenance hemodialysis

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.

Erythropoiesis Stimulatory Agent- Resistant Anemia in Dialysis Patients: Review of Causes and Management

“…A recent clinical study including 167 maintenance hemodialysis patients reported that patients with the ACE DD genotype had significantly lower ERI values compared to those with ACE II or ACE ID, independent of other traditional risk factors for anemia. Moreover, this study also revealed that the IL-1B-511CC genotype was significantly associated with lower ERI values in HD patients [21] .…”

ACE DDGenotype is Unfavorable to Korean Short-Term Muscle Power Athletes

“…There may be a diff erent contribution of functional ACE polymorphism on serum ACE activity. However, previous studies have reported that ACE insertion or deletion polymorphism represent serum ACE activity levels among Korea population; higher activity in D allele and lower ACE activity in I allele [18,31,47] . Therefore, we can speculate that the D allele is genetically linked with higher ACE activity than the I allele in our cohort.…”

Tumor necrosis factor-α and interleukin-1β gene polymorphisms and risk of brain abscess in North Indian population

“…IL-1b (À511 C < T) (rs no 16944) polymorphism was also detected by PCR using sense 5 0 -T GGCATTGATCTGGTTCATC-3 0 and antisense 5 0 -GTTTAGGAATCTTCC CACTT-3 0 primers with a PCR product of 304 bp. After restriction analysis with AvaI (Fermentas, New England Biolabs, Beverly, MA) at 37°C for 8 h, three genotypes could be distinguished: C/C (190 and 114 bp), C/T (340, 190 and 114 bp) and T/T (340 bp) [13]. All the results have been confirmed twice by PCR-RFLP and further results were validated by sequencing in 5% of samples.…”