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

Publication ,  Journal Article
George, S; Ruan, XZ; Navarrete, C; Turner, D; Reynard, M; Sweny, P; Hamilton, G; Wheeler, DC; Powis, SH; Moorhead, JF; Varghese, Z
Published in: Tissue Antigens
May 2004

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 these responses. The aim of this study was to determine whether cytokine 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-a, 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.

Duke Scholars

Published In

Tissue Antigens

DOI

ISSN

0001-2815

Publication Date

May 2004

Volume

63

Issue

5

Start / End Page

470 / 475

Location

England

Related Subject Headings

  • Renal Artery Obstruction
  • Polymorphism, Genetic
  • Middle Aged
  • Microsatellite Repeats
  • Interleukin-10
  • Immunology
  • Humans
  • Genotype
  • Genetic Predisposition to Disease
  • Aged
 

Citation

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George, S., Ruan, X. Z., Navarrete, C., Turner, D., Reynard, M., Sweny, P., … Varghese, Z. (2004). Renovascular disease is associated with low producer genotypes of the anti-inflammatory cytokine interleukin-10. Tissue Antigens, 63(5), 470–475. https://doi.org/10.1111/j.0001-2815.2004.00183.x
George, S., X. Z. Ruan, C. Navarrete, D. Turner, M. Reynard, P. Sweny, G. Hamilton, et al. “Renovascular disease is associated with low producer genotypes of the anti-inflammatory cytokine interleukin-10.Tissue Antigens 63, no. 5 (May 2004): 470–75. https://doi.org/10.1111/j.0001-2815.2004.00183.x.
George S, Ruan XZ, Navarrete C, Turner D, Reynard M, Sweny P, et al. Renovascular disease is associated with low producer genotypes of the anti-inflammatory cytokine interleukin-10. Tissue Antigens. 2004 May;63(5):470–5.
George, S., et al. “Renovascular disease is associated with low producer genotypes of the anti-inflammatory cytokine interleukin-10.Tissue Antigens, vol. 63, no. 5, May 2004, pp. 470–75. Pubmed, doi:10.1111/j.0001-2815.2004.00183.x.
George S, Ruan XZ, Navarrete C, Turner D, Reynard M, Sweny P, Hamilton G, Wheeler DC, Powis SH, Moorhead JF, Varghese Z. Renovascular disease is associated with low producer genotypes of the anti-inflammatory cytokine interleukin-10. Tissue Antigens. 2004 May;63(5):470–475.
Journal cover image

Published In

Tissue Antigens

DOI

ISSN

0001-2815

Publication Date

May 2004

Volume

63

Issue

5

Start / End Page

470 / 475

Location

England

Related Subject Headings

  • Renal Artery Obstruction
  • Polymorphism, Genetic
  • Middle Aged
  • Microsatellite Repeats
  • Interleukin-10
  • Immunology
  • Humans
  • Genotype
  • Genetic Predisposition to Disease
  • Aged