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

journal contribution
posted on 2023-05-17, 05:08 authored by Fowler, EV, Rajaraman Eri, Hume, G, Johnstone, S, Pandeya, N, Lincoln, D, Templeton, D, Radford-Smith, GL
Background: The cytokines tumour necrosis factor (TNF)α 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 TNFα (-308G/A, -857C/T) genes have been associated with altered levels of circulating IL10 and TNFα. Methods: We conducted an Australian boned 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 TNFα-857 with CD. Further investigation of a relationship with disease severity showed a significant association of higher producing IL10-1082G and TNFα-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 TNFα-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.

History

Publication title

Journal of Medical Genetics

Volume

42

Issue

6

Pagination

523-528

ISSN

1468-6244

Department/School

School of Health Sciences

Publisher

B M J Publishing Group

Place of publication

British Med Assoc House, Tavistock Square, London, England, Wc1H 9Jr

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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