Association of interferon-gamma +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-beta1 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.
Biolo
Gianni
G
University of Trieste, DSCMT, Clinica Medica, Ospedale di Cattinara, Strada di Fiume, 44734149 Trieste, Italy. biolo@units.it
Amoroso
Antonio
A
Savoldi
Silvana
S
Bosutti
Alessandra
A
Martone
Massimiliano
M
Pirulli
Doroti
D
Bianco
Francesco
F
Ulivi
Sheila
S
Bertok
Sara
S
Artero
Mary
M
Barazzoni
Rocco
R
Zanetti
Michela
M
Grassi
Gabriele
G
Guarnieri
Gianfranco
G
Panzetta
Giovanni
G
D000368:Aged; D000483:Alleles; D002097:C-Reactive Protein / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011336:Probability; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D006435:Renal Dialysis / Q000009:adverse effects / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D016207:Cytokines; D005819:Genetic Markers; D018836:Inflammation Mediators; D012333:RNA, Messenger; D007371:Interferon-gamma; D002097:C-Reactive Protein