Polymorphisms in two genes, IL-1B and ACE, are associated with erythropoietin resistance in Korean patients on maintenance hemodialysis.
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.
Jeong
Kyung Hwan
KH
Department of Nephrology, College of Medicine, Kyung Hee University, Seoul 130-702, Korea.
Lee
Tae Won
TW
Ihm
Chun Gyoo
CG
Lee
Sang Ho
SH
Moon
Ju Young
JY
D000328:Adult; D000368:Aged; D004351:Drug Resistance; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics*; D007723:Korea; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D006435:Renal Dialysis
D053583:Interleukin-1beta; D004921:Erythropoietin; D007703:Peptidyl-Dipeptidase A