NDT Advance Access originally published online on January 12, 2006
Nephrology Dialysis Transplantation 2006 21(5):1317-1322; doi:10.1093/ndt/gfk033
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Dialysis and Transplantation
Association of interferon-
+874A polymorphism with reduced long-term inflammatory response in haemodialysis patients
1 Dipartimento di Scienze Cliniche Morfologiche e Tecnologiche, Clinica Medica, 2 Dipartimento di Scienze della Riproduzione e dello Sviluppo, University of Trieste, Genetic Service, IRCCS Burlo Garofolo and3 S.C. di Nefrologia e Dialisi, Cattinara Hospital, Trieste, Italy
Correspondence and offprint requests to: Gianni Biolo, MD, PhD, University of Trieste, DSCMT, Clinica Medica, Ospedale di Cattinara, Strada di Fiume, 44734149 Trieste, Italy. Email: biolo{at}units.it
Background. We have studied the effects of interferon (IFN)-
allelic variations on expression levels of pro- and anti-inflammatory cytokines and on long-term inflammatory status in haemodialysis patients.
Methods. Genotyping was performed in 123 patients for single nucleotide polymorphisms in the first intron of the IFN- gene (+874 T/A). They were prospectively followed for 2 years. Cytokine mRNA levels in whole blood cells (detected by real time (RT)-PCR technique) and serum C-reactive protein (CRP) concentrations were compared in patient groups with different IFN- genotypes. Serum CRP was evaluated every month and inflammatory state was defined as percent of abnormal values (above 5 mg/l) over total determinations. Of the total, 102 patients survived and completed 24±1 monthly CRP determinations. The IFN- ±874 A/A, ‘low-producer’ genotype was associated with decreased (P<0.05) mRNA levels of IFN- and of interleukin-6 and with a lower (P<0.05) frequency of CRP elevation (37±6%) than the ±874 A/T and T/T, ‘intermediate and high-producer’ genotypes (59±6%, and 60±5%, respectively). The mRNA levels of tumor necrosis factor-
, IL-10 and of transforming growth factor-ß1 were not different in the three groups of patients. Pooled analysis in deceased (10±3 monthly CRP determinations) and survived patients confirmed the results obtained in the patients who completed the follow-up period.
Conclusions. The ‘low-producer’ IFN- +874 A/A genotype was associated with a preventive effect on long-term CRP elevation in haemodialysis patients possibly mediated by decreased gene expression of IFN- and IL-6.
Keywords: chronic renal failure; C-reactive protein; haemodialysis; inflammation; interferon-gamma; polymorphisms
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