Effect of Promoter Region Polymorphisms in the IP-10 Gene on HBsAg Loss in Chronic Hepatitis B Patients


Tutku Kaçar Şahin M., Burak Bereketoğlu M., Dogan H., Kose M., KUŞCU F., Kurtaran B., ...Daha Fazla

Hepatitis Monthly, cilt.25, sa.1, 2025 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 25 Sayı: 1
  • Basım Tarihi: 2025
  • Doi Numarası: 10.5812/hepatmon-160428
  • Dergi Adı: Hepatitis Monthly
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, CAB Abstracts, CINAHL, EMBASE, Veterinary Science Database
  • Anahtar Kelimeler: CXCL10, Cytokine, Hepatitis B Surface Antigen, IP-10 Protein, Polymorphisms
  • Çukurova Üniversitesi Adresli: Evet

Özet

Background: Although vaccination programs have significantly reduced the incidence of hepatitis B, chronic infection with the hepatitis B virus (HBV) continues to be a major contributor to liver-related morbidity and mortality. Among available therapeutic outcomes, the clearance of hepatitis B surface antigen (HBsAg) is considered the most favorable endpoint. Objectives: This study aims to evaluate genetic variations in the promoter region of the interferon gamma (IFN-γ)-inducible protein-10 (IP-10) gene — an important chemokine involved in inflammatory responses — which may play a role in the loss of HBsAg during chronic HBV infection. Methods: This research was designed as a single-center case-control study. The study included 60 patients with documented HBsAg loss, retrospectively identified from a cohort of 1,950 chronic hepatitis B patients who were followed at the Infectious Diseases and Clinical Microbiology outpatient clinic of Cukurova University Hospital between 2005 and 2022. A control group of 60 patients who remained HBsAg positive was also included. Peripheral blood samples were collected from all participants, and deoxyribonucleic acid (DNA) was extracted to analyze IP-10 gene polymorphisms. The target gene region was amplified using polymerase chain reaction (PCR), followed by Sanger sequencing. Based on data from the Genome-Wide Association Studies (GWAS) database and published literature, three variants located within the IP-10 promoter, exon 1, intron 1, and exon 2 regions were selected for analysis. The resulting sequence data (in .ab1 format) were analyzed using the CLC Genomics Workbench 24 software. Results: Between 2005 and 2022, the rate of HBsAg loss was calculated as 5.33%. The average age at which HBsAg loss occurred was 53.2 ± 11.3 years, and 85% of the individuals experienced this loss after the age of 40. When comparing the case and control groups, no statistically significant differences were found in terms of gender, current age, age at diagnosis, Body Mass Index, alcohol use, or smoking habits (P > 0.05). Three polymorphisms — c.-135C>T (rs56061981), c.85C>T (rs11548618), and c.83T>G — were detected within the promoter and exon 2 regions of the IP-10 gene. Analysis of genotype and allele distributions revealed no significant differences between the two groups for any of these variants (P > 0.05). Conclusions: Our findings suggest that the c.-135C>T, c.85C>T, and c.83T>G polymorphisms within the IP-10 gene region are not associated with HBsAg loss and therefore may not serve as reliable predictive markers.