LETTER TO JMG

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

E V Fowler^1,2, R Eri^1,*, G Hume^1,3, S Johnstone^1,, N Pandeya⁴, D Lincoln⁴, D Templeton³, G L Radford-Smith^1,3

¹ Inflammatory Bowel Diseases Laboratory, Clinical Research Centre, Royal Brisbane & Women’s Hospital Research Foundation, Queensland Institute of Medical Research, Brisbane, Australia
² School of Medicine, University of Queensland, Brisbane, Australia
³ Department of Gastroenterology, Royal Brisbane & Women’s Hospital, Brisbane, Australia
⁴ Cancer & Population Studies, Queensland Institute of Medical Research, Brisbane, Australia

Correspondence to:
Correspondence to:
Dr E V Fowler
Inflammatory Bowel Diseases Laboratory, Clinical Research Centre, Royal Brisbane & Women’s Hospital Research Foundation, Queensland Institute of Medical Research, Brisbane, Australia; bethf{at}qimr.edu.au

Background: The cytokines tumour necrosis factor (TNF) 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 (-308G/A, -857C/T) genes have been associated with altered levels of circulating IL10 and TNF.

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-857 with CD. Further investigation of a relationship with disease severity showed a significant association of higher producing IL10-1082G and TNF-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-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.

Keywords: Crohn’s disease; tumour necrosis factor ; interleukin 10; single nucleotide polymorphism; disease behaviour

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This article has been cited by other articles:

• Hume, G E, Fowler, E V, Lincoln, D, Eri, R, Templeton, D, Florin, T H, Cavanaugh, J A, Radford-Smith, G L (2006). Angiotensinogen and transforming growth factor {beta}1: novel genes in the pathogenesis of Crohn's disease.. J. Med. Genet. 43: e51-e51 [Abstract] [Full Text]