TNF alpha and IL10 SNPs act together to predict disease behaviour in Crohn's disease

Fowler, E. V., Eri, R., Hume, G., Johnstone, S., Pandeya, N., Lincoln, D., Templeton, D. and Radford-Smith, G. L. (2005) TNF alpha and IL10 SNPs act together to predict disease behaviour in Crohn's disease. Journal of Medical Genetics, 42 6: 523-528. doi:10.1136/jmg.2004.027425


Author Fowler, E. V.
Eri, R.
Hume, G.
Johnstone, S.
Pandeya, N.
Lincoln, D.
Templeton, D.
Radford-Smith, G. L.
Title TNF alpha and IL10 SNPs act together to predict disease behaviour in Crohn's disease
Journal name Journal of Medical Genetics   Check publisher's open access policy
ISSN 0022-2593
Publication date 2005-06-01
Sub-type Article (original research)
DOI 10.1136/jmg.2004.027425
Volume 42
Issue 6
Start page 523
End page 528
Total pages 6
Place of publication London
Publisher B M J Publishing Group
Collection year 2005
Language eng
Subject C1
1103 Clinical Sciences
Formatted abstract
Background:
The cytokines tumour necrosis factor (TNF){alpha} and interleukin (IL)10 have been implicated in the pathogenesis of Crohn’s disease (CD), with increased concentrations reported in patients with active disease. However, limited data exist on their effects on disease phenotype in the same population. Certain single nucleotide polymorphisms (SNPs) within the promoter region of the IL10 (-1082G/A, -592C/A) and TNF{alpha} (-308G/A, -857C/T) genes have been associated with altered levels of circulating IL10 and TNF{alpha}.

Methods:

We conducted an Australian based case–control study (304 CD patients; 231 healthy controls) of these four SNPs. Further investigation of two SNPs was conducted using a logistic regression analysis.

Results:

We identified a possible association of both IL10 SNPs and TNF{alpha}-857 with CD. Further investigation of a relationship with disease severity showed a significant association of higher producing IL10-1082G and TNF{alpha}-857C alleles with stricturing behaviour, which was strongest when these alleles were combined and persisted after multivariate analysis (p = 0.007; odds ratio (OR) 2.37, 95% CI 1.26 to 4.43). In addition, the TNF{alpha}-857CC genotype was independently associated with familial CD (p = 0.03; OR 3.12; 95% CI 1.15 to 8.46).

Conclusion:

These two SNPs may help to predict disease behaviour in CD patients, which may be clinically useful in shaping treatment of the disease at an earlier stage.
Keyword Genetics & Heredity
Inflammatory-bowel-disease
Necrosis-factor-alpha
Recombinant Human Interleukin-10
Intestinal Inflammation
Promoter Polymorphism
Variants
Gene
Susceptibility
Enterocolitis
Association
Q-Index Code C1
Additional Notes LETTER TO JMG

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
2006 Higher Education Research Data Collection
School of Medicine Publications
 
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