The IL-10R1 S138G loss-of-function allele and ulcerative colitis

P. Grundtner, S. Gruber, S. S. Murray, S. Vermeire, P. Rutgeerts, T. Decker, P. Lakatos, C. Gasche

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Genetic predisposition is a risk factor for the development of inflammatory bowel diseases (IBDs). Disruption of the interleukin (IL)-10 pathway in mice causes intestinal inflammation similar to human IBD. Two common non-synonymous IL-10R1 variants, S138G and G330R, were cloned and expressed in HeLa and Ba/F3. A reduction in IL-10-induced STAT1 and STAT3 activation was seen for IL-10R1-S138G (but not IL-10R1-G330R) by phosphospecific western blotting in both cell types. When analyzing 52 world populations for the presence of IL-10R1 variants, a strong dissimilarity was found between major geographical regions. In addition, when 182 IBD-parent trios were genotyped for both variants, a reduced transmission of haplotype -7 (carrying the S138G variant allele) to offspring with ulcerative colitis (UC) was observed. This UC-protective effect of S138G was confirmed in a Hungarian cohort (n = 185, allele frequency 11.6 versus 17.5%; P = 0.017) but not in an independent Belgian cohort (n = 666, allele frequency 15.9 versus 15.5%; P = 0.8). In conclusion, the IL-10R1 S138G variant is a loss-of-function allele for IL-10-induced STAT1 and STAT3 activation but does not protect from UC susceptibility.

Original languageEnglish
Pages (from-to)84-92
Number of pages9
JournalGenes and Immunity
Volume10
Issue number1
DOIs
Publication statusPublished - 2009

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Interleukins
Ulcerative Colitis
Alleles
Inflammatory Bowel Diseases
Interleukin-10
Gene Frequency
Genetic Predisposition to Disease
Haplotypes
Western Blotting
Inflammation
Population

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Grundtner, P., Gruber, S., Murray, S. S., Vermeire, S., Rutgeerts, P., Decker, T., ... Gasche, C. (2009). The IL-10R1 S138G loss-of-function allele and ulcerative colitis. Genes and Immunity, 10(1), 84-92. https://doi.org/10.1038/gene.2008.72

The IL-10R1 S138G loss-of-function allele and ulcerative colitis. / Grundtner, P.; Gruber, S.; Murray, S. S.; Vermeire, S.; Rutgeerts, P.; Decker, T.; Lakatos, P.; Gasche, C.

In: Genes and Immunity, Vol. 10, No. 1, 2009, p. 84-92.

Research output: Contribution to journalArticle

Grundtner, P, Gruber, S, Murray, SS, Vermeire, S, Rutgeerts, P, Decker, T, Lakatos, P & Gasche, C 2009, 'The IL-10R1 S138G loss-of-function allele and ulcerative colitis', Genes and Immunity, vol. 10, no. 1, pp. 84-92. https://doi.org/10.1038/gene.2008.72
Grundtner P, Gruber S, Murray SS, Vermeire S, Rutgeerts P, Decker T et al. The IL-10R1 S138G loss-of-function allele and ulcerative colitis. Genes and Immunity. 2009;10(1):84-92. https://doi.org/10.1038/gene.2008.72
Grundtner, P. ; Gruber, S. ; Murray, S. S. ; Vermeire, S. ; Rutgeerts, P. ; Decker, T. ; Lakatos, P. ; Gasche, C. / The IL-10R1 S138G loss-of-function allele and ulcerative colitis. In: Genes and Immunity. 2009 ; Vol. 10, No. 1. pp. 84-92.
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abstract = "Genetic predisposition is a risk factor for the development of inflammatory bowel diseases (IBDs). Disruption of the interleukin (IL)-10 pathway in mice causes intestinal inflammation similar to human IBD. Two common non-synonymous IL-10R1 variants, S138G and G330R, were cloned and expressed in HeLa and Ba/F3. A reduction in IL-10-induced STAT1 and STAT3 activation was seen for IL-10R1-S138G (but not IL-10R1-G330R) by phosphospecific western blotting in both cell types. When analyzing 52 world populations for the presence of IL-10R1 variants, a strong dissimilarity was found between major geographical regions. In addition, when 182 IBD-parent trios were genotyped for both variants, a reduced transmission of haplotype -7 (carrying the S138G variant allele) to offspring with ulcerative colitis (UC) was observed. This UC-protective effect of S138G was confirmed in a Hungarian cohort (n = 185, allele frequency 11.6 versus 17.5{\%}; P = 0.017) but not in an independent Belgian cohort (n = 666, allele frequency 15.9 versus 15.5{\%}; P = 0.8). In conclusion, the IL-10R1 S138G variant is a loss-of-function allele for IL-10-induced STAT1 and STAT3 activation but does not protect from UC susceptibility.",
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