Association between host TNF-α, TGF-β1, p53 polymorphisms, HBV X gene mutation, HBV viral load and the progression of HBV-associated chronic liver disease in Indonesian patients

Citrawati Dyah Kencono Wungu; Mochamad Amin; S Eriaty N Ruslan; Priyo Budi Purwono; Ulfa Kholili; Ummi Maimunah; Poernomo Boedi Setiawan; Maria Inge Lusida; Soetjipto Soetjipto; Retno Handajani

doi:10.3892/br.2019.1239

Association between host TNF-α, TGF-β1, p53 polymorphisms, HBV X gene mutation, HBV viral load and the progression of HBV-associated chronic liver disease in Indonesian patients

Biomed Rep. 2019 Oct;11(4):145-153. doi: 10.3892/br.2019.1239. Epub 2019 Sep 9.

Authors

Citrawati Dyah Kencono Wungu^{1

2}, Mochamad Amin², S Eriaty N Ruslan², Priyo Budi Purwono³, Ulfa Kholili⁴, Ummi Maimunah⁴, Poernomo Boedi Setiawan^{2

3}, Maria Inge Lusida^{2

3}, Soetjipto Soetjipto^{1

2}, Retno Handajani^{1

2}

Affiliations

¹ Department of Medical Biochemistry, Faculty of Medicine, University of Airlangga, Surabaya 60131, Indonesia.
² Institute of Tropical Disease, University of Airlangga Campus C, Mulyorejo, Surabaya 60286, Indonesia.
³ Department of Medical Microbiology, Faculty of Medicine, University of Airlangga, Surabaya 60131, Indonesia.
⁴ Department of Internal Medicine, Faculty of Medicine, University of Airlangga, Dr Soetomo General Hospital, Surabaya 60286, Indonesia.

Abstract

In developing countries, including Indonesia, there is a high mortality rate associated with the progression of hepatitis B virus (HBV)-associated chronic liver disease (CLD). The pathogenesis of HBV infection is influenced by viral and host factors. To determine potential associations between these factors, host single nucleotide polymorphisms (SNPs) on TNF-α, TGF-β1 and p53, HBV X gene mutation and HBV viral load were investigated in patients with HBV-associated CLD in Surabaya, Indonesia. Sera were collected from 87 CLD patients with HBV infection. TNF-α, TGF-β1 and p53 SNPs were genotyped by PCR restriction fragment length polymorphism. The HBV X gene was sequenced and compared with reference strains to determine mutations and the viral load was measured using reverse transcription-quantitative PCR. In Indonesian patients, no association between TNF-α, TGF-β1 and p53 SNPs and CLD or X gene mutation were identified. A total of 23% (20/87) of samples had HBV X gene mutations, including ten substitution types, one deletion and one insertion. Multinomial regression analysis revealed that the K130M/V131I mutations were correlated with CLD progression (OR, 7.629; 95% CI, 1.578-36.884). Significant differences in viral load were found in HBV-infected patients who had X gene mutations, such as R87W/G, I127L/T/N/S and K130M/V131I mutations (P<0.05). The presence of K130M and V131I mutations may be predictive for the progression of HBV-associated CLD in Indonesia.

Keywords: X gene mutation; chronic liver disease; hepatitis B virus; host genetic polymorphism.