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

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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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Acknowledgment

The work was funded by the grant-in-aid by the Department of Science and Technology, New Delhi, India. DA, PK, and RS are thankful to the Department of Biotechnology, Council of Medical Research, and Council of Scientific and Industrial Research, New Delhi, India for Senior Research Fellowship, respectively.

Conflict of Interest

We have no conflict of interest.

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Authors and Affiliations

  1. Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, Uttar Pradesh, India

    Dinesh K. Ahirwar, Pravin Kesarwani, Ranjana Singh & Rama Devi Mittal

  2. Department of Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, Uttar Pradesh, India

    Uday Chand Ghoshal

Authors
  1. Dinesh K. Ahirwar
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  2. Pravin Kesarwani
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  3. Ranjana Singh
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  4. Uday Chand Ghoshal
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  5. Rama Devi Mittal
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Correspondence to Rama Devi Mittal.

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Ahirwar, D.K., Kesarwani, P., Singh, R. et al. Role of Tumor Necrosis Factor-Alpha (C-863A) Polymorphism in Pathogenesis of Inflammatory Bowel Disease in Northern India. J Gastrointest Canc 43, 196–204 (2012). https://doi.org/10.1007/s12029-010-9238-9

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