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Molecular and Cellular Biochemistry

, Volume 385, Issue 1–2, pp 297–307 | Cite as

IFN-γ (+874) and not TNF-α (−308) is associated with HBV-HCC risk in India

  • Roli Saxena
  • Yogesh Kumar Chawla
  • Indu Verma
  • Jyotdeep Kaur
Article

Abstract

Tumor necrosis factor (TNF)-α and interferon (IFN)-γ, the pro-inflammatory Th1 cytokines are the indispensable coordinators of the inflammatory responses involved in hepatitis B virus (HBV) pathogenesis. This study attempted to evaluate any possible association among TNF-α (−308G>A) and IFN-γ (+874T/A) genotypes, the spontaneous blood and mRNA levels and expression of their major signal transducers, namely STAT1 and NF-кB with hepatitis B virus-induced hepatocellular carcinoma (HCC) susceptibility in India. For this, 398 subjects (146 controls, 68 inactive-HBV-carriers, 64 chronic-active HBV patients, 61 HBV-cirrhotics, and 59 HBV-HCC subjects) were enrolled. Polymerase chain reaction–restriction fragment length polymorphism, allele-specific PCR, enzyme-linked immunosorbent assay, reverse transcriptase-PCR, and Western blot analysis were done for assessing polymorphism, blood levels, mRNA expression, and protein expression of signal transducers, respectively, of TNF-α and IFN-γ. The study revealed no significant association of TNF-α (−308) GA genotype, while a significant negative association of IFN-γ (+874) TA and AA genotypes, in HBV-HCC risk. Moreover, blood levels of TNF-α were significantly elevated as disease progresses to HCC, while IFN-γ levels were raised in HCC patients only. Besides, IFN-γ mRNA levels were significantly elevated in cirrhotics, with no change observed in TNF-α transcript levels. Moreover, NF-кB expression also consistently increased during HCC progression. These observations suggest a vital negative association of IFN-γ (+874) with HBV-HCC risk, with no significant association evident in TNF-α (−308). However, the TNF-α and IFN-γ levels markedly increased in HCC development.

Keywords

TNF-α IFN-γ HBV HCC 

Notes

Acknowledgments

The financial assistance by Indian Council of Medical Research (ICMR) is highly acknowledged.

Disclosure

No competing financial interests exist.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Roli Saxena
    • 1
  • Yogesh Kumar Chawla
    • 2
  • Indu Verma
    • 1
  • Jyotdeep Kaur
    • 1
  1. 1.Department of BiochemistryPostgraduate Institute of Medical Education and ResearchChandigarhIndia
  2. 2.Department of HepatologyPostgraduate Institute of Medical Education and ResearchChandigarhIndia

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