Journal Article

Association of interferon-γ +874A polymorphism with reduced long-term inflammatory response in haemodialysis patients

Gianni Biolo, Antonio Amoroso, Silvana Savoldi, Alessandra Bosutti, Massimiliano Martone, Doroti Pirulli, Francesco Bianco, Sheila Ulivi, Sara Bertok, Mary Artero, Rocco Barazzoni, Michela Zanetti, Gabriele Grassi, Gianfranco Guarnieri and Giovanni Panzetta

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 21, issue 5, pages 1317-1322
Published in print May 2006 | ISSN: 0931-0509
Published online January 2006 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfk033
Association of interferon-γ +874A polymorphism with reduced long-term inflammatory response in haemodialysis patients

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Background. We have studied the effects of interferon (IFN)-γ 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-γ 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-γ 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-γ ±874 A/A, ‘low-producer’ genotype was associated with decreased (P<0.05) mRNA levels of IFN-γ 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-α, IL-10 and of transforming growth factor-β1 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-γ +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-γ and IL-6.

Keywords: chronic renal failure; C-reactive protein; haemodialysis; inflammation; interferon-gamma; polymorphisms

Journal Article.  3789 words.  Illustrated.

Subjects: Nephrology

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