The IL-10R1 S138G loss-of-function allele and ulcerative colitis.
Genes Immun
; 10(1): 84-92, 2009 Jan.
Article
em En
| MEDLINE
| ID: mdl-18800073
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Colite Ulcerativa
/
Predisposição Genética para Doença
/
Alelos
/
Receptores de Interleucina-10
Tipo de estudo:
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2009
Tipo de documento:
Article