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Erschienen in: Journal of Gastrointestinal Cancer 2/2012

01.06.2012 | Original Article

Role of Tumor Necrosis Factor-Alpha (C-863A) Polymorphism in Pathogenesis of Inflammatory Bowel Disease in Northern India

verfasst von: Dinesh K. Ahirwar, Pravin Kesarwani, Ranjana Singh, Uday Chand Ghoshal, Rama Devi Mittal

Erschienen in: Journal of Gastrointestinal Cancer | Ausgabe 2/2012

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Abstract

Objective

Inflammatory bowel diseases (IBDs), namely ulcerative colitis (UC) and Crohn’s disease (CD), are characterized by chronic and idiopathic inflammatory conditions of gastrointestinal tract that are immunologically mediated. Single nucleotide polymorphisms in cytokine genes have been reported to modulate inflammation. Therefore, we analyzed the association of pro/anti-inflammatory cytokine genes polymorphism with IBD susceptibility.

Methods

Genotyping of interleukin (IL)-4 repeat polymorphism in intron-3, IL-10 (G-1082A and C-819T), and tumor necrosis factor-alpha (TNF-A) (−1031 T>C, −863 C>A, and −857 C>T) was performed in 153 patients with IBD and in 207 controls.

Results

TNF-A −863 AA genotype was associated with enhanced IBD susceptibility (odds ratio (OR), 4.82; 95% confidence interval (CI), 2.60–8.96), more so for UC (OR, 5.79; 95% CI, 2.99–11.21), Crohn’s disease [CD] (OR, 3.13; 95% CI, 1.16–8.47). TNF-A T/C/T (OR, 4.40; 95% CI, 1.64–11.81) and C/A/C (OR, 4.15; 95% CI, 2.48–6.96) haplotypes were associated with increased IBD risk. The frequency of IL-4, B2 carrier (B1/B2 + B2/B2) was significantly lower in left-sided UC (17.1%) than proctosigmoiditis (47.6%); p, 0.016. In contrast, TNF-A −863 AA genotype frequency was much higher in pancolitis (45.5) than in proctosigmoiditis (14.2); p, 0.037. Variant genotypes of IL-4 (B1/B2 + B2/B2) were absent in colonic type CD. IL-10 polymorphisms did not demonstrate any association with IBD. None of the polymorphisms were associated with steroid treatment and surgery.

Conclusion

The present study depicts that high-producing genotype of TNF-A (−863 AA) was associated with increased risk of IBD more so with UC. Similarly, combined effect of TNF-A polymorphisms in haplotype analysis demonstrated additively increased risk of IBD.
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Metadaten
Titel
Role of Tumor Necrosis Factor-Alpha (C-863A) Polymorphism in Pathogenesis of Inflammatory Bowel Disease in Northern India
verfasst von
Dinesh K. Ahirwar
Pravin Kesarwani
Ranjana Singh
Uday Chand Ghoshal
Rama Devi Mittal
Publikationsdatum
01.06.2012
Verlag
Springer US
Erschienen in
Journal of Gastrointestinal Cancer / Ausgabe 2/2012
Print ISSN: 1941-6628
Elektronische ISSN: 1941-6636
DOI
https://doi.org/10.1007/s12029-010-9238-9

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