Association of interleukin-18 genotypes (−607C > A) and (−137 G > C) with the hepatitis B virus disease progression to hepatocellular carcinoma
Autor: | Jyotdeep Kaur, Stuti Agarwal, Deepti More, Roli Saxena, R. P. Ola, Yogesh Chawla, Isha Rani, Renuka Sharma, Taqveema Ali |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Hepatitis B virus business.industry Clinical Biochemistry Single-nucleotide polymorphism Cell Biology General Medicine medicine.disease medicine.disease_cause digestive system diseases Pathogenesis 03 medical and health sciences 030104 developmental biology 0302 clinical medicine 030220 oncology & carcinogenesis Hepatocellular carcinoma Genotype Immunology medicine Biomarker (medicine) Interleukin 18 Risk factor business Molecular Biology |
Zdroj: | Molecular and Cellular Biochemistry. 476:3923-3933 |
ISSN: | 1573-4919 0300-8177 |
Popis: | 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. |
Databáze: | OpenAIRE |
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