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Association of interleukin-18 genotypes (−607C > A) and (−137 G > C) with the hepatitis B virus disease progression to hepatocellular carcinoma

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Abstract

Chronic infection with HBV has been reported to be associated with the development of HCC. The inflammation mounted by cytokine-mediated immune system plays an important role in the pathogenesis of HBV-associated HCC. IL-18 is a pro-inflammatory cytokine whose role in the development of HBV-associated chronic to malignant disease state has not been much studied. The present study was conceived to determine the role of genetic polymorphisms in IL-18, serum levels of IL-18, and expression level of its signal transducers in the HBV disease progression. A total of 403 subjects were enrolled for this study including 102 healthy subjects and 301 patients with HBV infection in different diseased categories. Polymorphism was determined using PCR–RFLP. Genotypic distributions between the groups were compared using odd’s ratio and 95% CI were calculated to express the relative risk. Circulating IL-18 levels were determined by ELISA. Expression levels of pSTAT-1 and pNFƙB was determined by western blotting. In case of IL-18(− 607C > A), the heterozygous genotype (CA) was found to be a protective factor while in case of IL-18(− 137G > C) the heterozygous genotype (GC) acted as a risk factor for disease progression from HBV to HCC. Moreover, serum IL-18 levels were significantly increased during HBV disease progression to HCC as compared to controls. Also the levels of activated signal transducers (pSTAT-1 and pNF-κB) of IL-18 in stimulated PBMCs were significantly increased during HBV to HCC disease progression. These findings suggest that IL-18 has the potential to act as a biomarker of HBV-related disease progression to HCC.

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Abbreviations

HCC:

Hepatocellular carcinoma

HBV:

Hepatitis B virus

HCV:

Hepatitis C virus

ROIs:

Reactive oxygen intermediates

NO:

Nitric oxide

PBMCs:

Peripheral blood mononuclear cells;

pSTAT-1:

Phosphorylated signal transducer and activator of transcription

NF-κB:

Phosphorylated signal transducer and activator of transcription

PCR–RFLP:

Polymerase chain reaction-restriction fragment length polymorphism

IFN-γ:

Interferon gamma

SNPs:

Single nucleotide polymorphisms

HBeAG:

Hepatitis B e-antigen

CHB:

Chronic hepatitis B

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Acknowledgements

We express our immense gratitude to the participants and their families. The contribution of MrChander Mohan and Mr Gurpreet Singh, laboratory technologists is duly acknowledged. We acknowledge the financial support (Grant Number: SR/S0/HS-0043/2012) from Department of Science and Technology (DST), New Delhi

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Authors and Affiliations

  1. Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Taqveema Ali, Roli Saxena, Isha Rani, Renuka Sharma, Deepti More, Rajendra Ola, Stuti Agarwal & Jyotdeep Kaur

  2. Department of Hepatology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India

    Yogesh Kumar Chawla

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  1. Taqveema Ali
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  2. Roli Saxena
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Contributions

JK and RS planned the study. YKC enrolled and diagnosed the patients. Sample collection was done by TA and RS. TA, RS, IR, RS, DM, RO, and SA performed experiments and collected data. JK and TA analyzed and interpreted data. JK and TA drafted manuscript and all the authors approved the draft of the submitted manuscript.

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Correspondence to Jyotdeep Kaur.

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Ali, T., Saxena, R., Rani, I. et al. Association of interleukin-18 genotypes (−607C > A) and (−137 G > C) with the hepatitis B virus disease progression to hepatocellular carcinoma. Mol Cell Biochem 476, 3923–3933 (2021). https://doi.org/10.1007/s11010-021-04206-1

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