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

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.