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

Background. We have studied the effects of interferon (IFN)-gamma 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-gamma 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-gamma 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-gamma +/- 874 A/A, 'low-producer' genotype was associated with decreased (P < 0.05) mRNA levels of IFN-gamma 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-alpha, IL-10 and of transforming growth factor-beta 1 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-gamma +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-gamma and IL-6.