期刊
EXPERIMENTAL AND MOLECULAR MEDICINE
卷 40, 期 2, 页码 161-166出版社
NATURE PUBLISHING GROUP
DOI: 10.3858/emm.2008.40.2.161
关键词
end stage renal disease; erythropoietin; interleukin-1 beta; kidney failure; chronic; peptidyl-di-peptidase A; polymorphism; genetic
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 (ER1) 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-511 C/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.
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