Role of tumor necrosis factor-alpha (C-863A) polymorphism in pathogenesis of inflammatory bowel disease in Northern India.
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.


CONCLUSIONS
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.
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, Uttar Pradesh, India.
Dinesh K
DK
Ahirwar
Pravin
P
Kesarwani
Ranjana
R
Singh
Uday Chand
UC
Ghoshal
Rama Devi
RD
Mittal
D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007194:India; D015212:Inflammatory Bowel Diseases / Q000235:genetics*; D016753:Interleukin-10 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D015847:Interleukin-4
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