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Renovascular disease is associated with low producer genotypes of the anti-inflammatory cytokine interleukin-10

George, S; Ruan, XZ; Navarrete, C; Turner, D; Reynard, M; Sweny, P; ... Varghese, Z; + view all (2004) Renovascular disease is associated with low producer genotypes of the anti-inflammatory cytokine interleukin-10. TISSUE ANTIGENS , 63 (5) 470 - 475.

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Abstract

Cytokines are important mediators of inflammatory and proliferative responses in disease states including atherosclerosis. Genetic variations in cytokine production could potentially influence the outcome of The aim of this study was to determine whether cytokine these responses gene polymorphism might influence the development of atherosclerotic renal artery stenosis. Sixty-six patients with atherosclerotic renal artery stenosis and 100 normal healthy individuals were genotyped for interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-2 promoter region polymorphism. TNF-alpha, TNF-d, and IL-10 microsatellite polymorphisms were also analyzed. The frequency of the anti-inflammatory cytokine IL-10 promoter (-1082 A positive) GA and AA genotypes which are associated with low production were higher in the patient group when compared to the control group. The AA-TT-AA homozygous genotype combination of three single-nucleotide polymorphisms at -1082, -819, and -592 in the IL-10 gene was also observed at a higher frequency in the patient group compared to the controls. The frequency of TNF-alpha, IL-6, and IL-2 polymorphisms did not show any significant difference between the patient and control groups. To correlate IL-10 genotypes with differences in IL-10 protein expression, in vitro mRNA and protein levels were analyzed in lipopolysaccharide-stimulated peripheral blood mononuclear cells from 22 patients with renal artery stenosis and 33 controls. Individuals genotyped as A positive at position -1082 produced lower levels of IL-10 protein and had lower copy numbers of mRNA when compared to individuals genotyped as A negative in both patient and control groups. The increased frequency of the low producer IL-10 promoter, -1082 A-positive genotype in patients with renal artery stenosis, suggests that IL-10 may protect against the development of atherosclerotic renovascular disease.

Type:Article
Title:Renovascular disease is associated with low producer genotypes of the anti-inflammatory cytokine interleukin-10
Keywords:atherosclerosis, cytokine polymorphism, renal artery stenosis, NECROSIS-FACTOR-ALPHA, SYSTEMIC-LUPUS-ERYTHEMATOSUS, HEMODIALYSIS-PATIENTS, TNF-ALPHA, INFLAMMATORY CYTOKINES, RENAL-TRANSPLANTATION, MONONUCLEAR-CELLS, IL-10 PROMOTER, GENE PROMOTER, IFN-GAMMA
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Internal Medicine
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of)

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