Analysis of polymorphisms of tumor necrosis factor-α and polymorphic xenobiotic metabolizing enzymes in inflammatory bowel disease: Study from northern India

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Journal of Gastroenterology and Hepatology

Volume 22 Issue 6 Page 920Issue 6 - 924 - June 2007

To cite this article: Rama D Mittal, Parmeet K Manchanda, Hemant K Bid, Uday C Ghoshal (2007) Analysis of polymorphisms of tumor necrosis factor-α and polymorphic xenobiotic metabolizing enzymes in inflammatory bowel disease: Study from northern India Journal of Gastroenterology and Hepatology 22 (6), 920–924. doi:10.1111/j.1440-1746.2006.04538.x

GASTROENTEROLOGY

Analysis of polymorphisms of tumor necrosis factor-α and polymorphic xenobiotic metabolizing enzymes in inflammatory bowel disease: Study from northern India

Rama D Mittal,*Departments of *Urology andDr Rama Devi Mittal, Additional Professor (Biochemistry), Department of Urology, SGPGIMS, Raebareli Road, Lucknow-226014, India.Email: rmittal@... or ramamittal@...

Parmeet K Manchanda,*Departments of *Urology and Hemant K Bid*Departments of *Urology and and Uday C GhoshalGastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Departments of *Urology and Gastroenterology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India

Dr Rama Devi Mittal, Additional Professor (Biochemistry), Department of Urology, SGPGIMS, Raebareli Road, Lucknow-226014, India.Email: rmittal@... or ramamittal@...

Abstract

Background: Tumor necrosis factor (TNF)-α is a proinflammatory cytokine associated with inflammatory diseases, while GSTM1 and T1 enzymes catalyze detoxification of products of oxidative stress and hence reduce inflammation. Thus, both may play important roles in the pathogenesis of inflammatory bowel disease (IBD). The present study aimed to evaluate the effect of polymorphism of the TNF-α promoter at the −308 site, GSTM1 and GSTT1 in patients with IBD and healthy controls from northern India.

Method: Genotyping was performed in 114 patients with IBD (22 Crohn’s disease [CD] and 92 ulcerative colitis [uC]) in TNF-α and 105 (20 CD and 85 UC) in GSTM1 and T1 and 164 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and multiplex PCR methods.

Results: Patients with IBD were comparable to healthy controls in relation to age and gender. Genotypic and allelic frequencies of TNF-α were comparable among patients with IBD and healthy controls. GSTM1 null genotype was more frequent in UC than in healthy controls (52/85 vs 49/164; P < 0.001) and GSTT1 null genotype was more frequent both in UC and CD as compared to healthy controls (77/85 and 18/20 vs 26/164, respectively; P < 0.001 for both). Frequency of combined null genotype in GSTM1 and T1 was more frequently associated with IBD than healthy controls (4/20 vs 8/164; P = 0.029, OR = 4.875 and 28/85 vs 8/164; P < 0.001, OR = 9.579, respectively).

Conclusions: ‘Null’ genotypes of GSTM1 and T1 are associated with IBD and the combination of the two GST genotypes further increases the risk, possibly due to gene–gene interaction. TNF-α is unlikely to be an important determinant of susceptibility to IBD in the Indian population.