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

Abstract

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. © 2006 Oxford University Press.