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Association of Tumor Necrosis Factor-Alpha Gene Promoter Polymorphisms with Acute Viral Hepatitis in the Indian Population

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Abstract

The key elements that determine the host response to either the self-limited or a severe fulminant form of liver disease are unclear. We have investigated the potential association of single nucleotide polymorphisms (SNPs) in the promoter region of tumor necrosis factor-alpha (TNFα) in their susceptibility to acute viral hepatitis (AVH) and fulminant hepatic failure (FHF) patients exhibiting specific viral etiology. A total of 124 individuals including 64 cases comprising 27 FHF, 37 AVH, and 60 healthy controls were recruited. SNPs at −238 (G/A), −308 (G/A), −857 (C/T), and −863 (C/A) of TNFα were detected by polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) and confirmed by direct sequencing. Serum levels of TNFα were determined at admission and death or recovery. Association between the TNFα genotype and susceptibility to FHF was not evident; however, carrier genotypes in relation to the −308 (GA/AA) and −857 (CT/TT) loci were found to be significantly (P ≤ 0.05) associated with susceptibility to AVH in relation to controls. The mean TNFα serum levels at admission were significantly higher (P < 0.001) in FHF than AVH patients, but no marked difference was observed between FHF-E (expired; n = 17) and FHF-S (survivors; n = 10), though the former were comparatively higher. This study suggests that SNPs at −308 and −857 of the TNFα promoter may represent an increased risk for the development of AVH but not for FHF in the Indian population.

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Acknowledgments

The study was supported by internal funding at the study centers. There are no conflicts of interest with any of the authors. The study has been presented at the American College of Gastroenterology Annual Scientific Meeting and Postgraduate Course, Las Vegas, Nevada, October 2006. The manuscript has not been submitted or accepted elsewhere. All authors have contributed to, seen, and approved the final, submitted version of the manuscript.

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Authors and Affiliations

  1. Division of Gastroenterology, Department of Medicine, Maulana Azad Medical College and Lok Nayak Hospital, BL Taneja Block, BSZ Marg, New Delhi, 110001, India

    Shashideep Singhal & Premashis Kar

  2. Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICPO), ICMR, I-7/SECTOR-39, Noida, Uttar Pradesh, 201301, India

    Indu Kohaar & Mausumi Bharadwaj

  3. Division of Non-Communicable Diseases, ICMR, Delhi, India

    Deepak K. Shukla

  4. Division of Molecular Oncology, Institute of Cytology & Preventive Oncology (ICPO), ICMR, Noida, Uttar Pradesh, India

    Bhudev C. Das

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  1. Shashideep Singhal
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  2. Indu Kohaar
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  3. Mausumi Bharadwaj
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Correspondence to Premashis Kar.

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Singhal, S., Kohaar, I., Bharadwaj, M. et al. Association of Tumor Necrosis Factor-Alpha Gene Promoter Polymorphisms with Acute Viral Hepatitis in the Indian Population. Dig Dis Sci 55, 1106–1112 (2010). https://doi.org/10.1007/s10620-009-0799-z

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  • DOI: https://doi.org/10.1007/s10620-009-0799-z

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