Genetic associations of vitamin D receptor polymorphisms with advanced liver fibrosis and response to pegylated interferon-based therapy in chronic hepatitis C
Kessarin Thanapirom,
Sirinporn Suksawatamnuay,
Wattana Sukeepaisarnjaroen,
Pisit Tangkijvanich,
Panarat Thaimai,
Rujipat Wasitthankasem,
Yong Poovorawan,
Piyawat Komolmit
Affiliations
Kessarin Thanapirom
Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
Sirinporn Suksawatamnuay
Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
Wattana Sukeepaisarnjaroen
Department of Medicine, Srinagarind Hospital, Faculty of Medicine, Khon Kaen University, Gastroenterology unit, Khon Kaen, Thailand
Pisit Tangkijvanich
Faculty of Medicine, Chulalongkorn University, Department of Biochemistry, Bangkok, Thailand
Panarat Thaimai
Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
Rujipat Wasitthankasem
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Center of Excellence in Clinical Virology, Bangkok, Thailand
Yong Poovorawan
Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Center of Excellence in Clinical Virology, Bangkok, Thailand
Piyawat Komolmit
Division of Gastroenterology and Hepatology, Department of Medicine, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Thai Red Cross Society, Bangkok, Thailand
Vitamin D receptor (VDR) modulates host immune responses to infections such as hepatitis C virus (HCV) infection, including interferon signaling. This study aimed to investigate the associations of VDR polymorphisms with advanced liver fibrosis and response to pegylated interferon (PEG-IFN)-based therapy in patients with chronic HCV infection. In total, 554 Thai patients with chronic HCV infection treated with a PEG-IFN-based regimen were enrolled. Six single-nucleotide polymorphisms (SNPs) were genotyped: the IL28B C > T (rs12979860) SNP and five VDR SNPs, comprising FokI T > C (rs2228570), BsmI C > T (rs1544410), Tru9I G > A (rs757343), ApaI C > A (rs7975232), and TaqI A > G (rs731236). In total, 334 patients (60.3%) achieved sustained virological response (SVR), and 255 patients (46%) were infected with HCV genotype 1. The bAt (CCA) haplotype, consisting of the BsmI rs1544410 C, ApaI rs7975232 C, and TaqI rs731236 A alleles, was associated with poor response (in terms of lack of an SVR) to PEG-IFN-based therapy. The IL28B rs12979860 CT/TT genotypes (OR = 3.44, 95% CI [2.12–5.58], p 3.25. VDR polymorphisms were not associated with pre-treatment serum HCV RNA. In Thai patients with chronic HCV infection, the bAt haplotype is associated with poor response to PEG-IFN-based therapy, and the FokI rs2228570 TT/TC genotypes are risk factors for advanced liver fibrosis.
