Association of SCARB1 Gene Polymorphisms with Virological Response in Chronic Hepatitis C Patients Receiving Pegylated Interferon plus Ribavirin Therapy

Abstract

The scavenger receptor type B class I(SR-BI) is a receptor for high-density lipoproteins(HDL) and one of entry factors for hepatitis C virus(HCV). We examined the association of single nucleotide polymorphisms(SNPs) of the SCARB1 gene, which encodes SR-BI, with virologic responses to pegylated interferon-based treatment in Asian chronic hepatitis C(CHC) patients. Human genomic and clinical data were collected from 156 consecutive Taiwanese HCV genotype 1 or 2 patients who received pegylated interferon plus ribavirin therapy and 153 non-HCV healthy subjects. Three SNPs(rs10846744, rs5888, and rs3782287) of the SCARB1 gene that have been linked to humans diseases were investigated. rs10846744 rather than rs5888 or rs3782287 was associated with serum HCV RNA level and sustained virologic response(SVR) to pegylated interferon plus ribavirin therapy in CHC patients(GG vs. non-GG genotype, Adjusted Odds Ratio, 95% CI: 0.32, 0.11–0.95, P = 0.039). Among patients with IL28B rs8099917 non-TT genotypes, those with rs10846744 non-GG genotype had a higher SVR rate than those with GG genotypes. In addition, patients with GG genotype had a higher fasting blood glucose level than those with CC genotype. In conclusion, SCARB1 gene polymorphisms may serve as a potential predictor of treatment responses in CHC patients receiving interferon-based therapy. (ClinicalTrials.gov number, NCT02714712).

Scavenger Receptors: Novel Roles in the Pathogenesis of Liver Inflammation and Cancer

“… 122 Consequently, SCARB1 is strongly implicated in the pathogenesis of viral hepatitis and this is emphasized by the fact that patients with genetic variants of SCARB1 exhibit altered viral load 123 and virological responses. 124 125 Nevertheless, therapeutic targeting of SCARB1 with an antagonist in early-phase clinical trials demonstrated relatively low efficacy in HCV patients, suggesting a certain level of redundancy in its role. 126 127 In addition, and consistent with scavenger receptors being considered PRRs, one study has implicated both SR-AI and SCARF1 in the uptake and cross-presentation of HCV nonstructural (NS)3 protein by human myeloid cells (dendritic cells [DCs] and monocytes).…”

IFNL4 haplotype, linkage disequilibrium and their influence on virological response to hepatitis C virus infection in Indian population

“…In previous reports, IFNL4 variants such as the major CC genotype of rs12979860, TT genotype of rs8099917 [30] and DG allele at rs368234815 [1] were found to be associated with spontaneous clearance of virus in individuals with acute HCV infection. Polymorphisms of other genes such as virus entry related SCARB1 gene [14] and MxA gene-rs2071430 TT genotype [32] also have shown association with spontaneous clearance or impaired clearance to HCV infections.…”

“…Genetic association of single nucleotide polymorphisms (SNPs) with HCV infections are mostly related to the host genes responsible for antiviral response or virus entry which either improve treatment induced clearance or promote/impair virus clearance against acute/chronic infections. In a recent study, HCV entry related SCARB1 (scavenger receptor type B class I) gene polymorphism was found to be associated with HCV RNA level and therapeutic response [14]. In earlier studies, IL28b polymorphisms (rs12979860G/C and rs8099917C/T) were found to be associated with sustained virological response (SVR) to pegylated IFN and ribavirin (PEG-IFN/RBV) therapy in both genome wide and candidate gene approach studies [10,29].…”

SCARB1 variants and HCV infection: Host susceptibility is lost in translation

“…6 In contrast, the rs10846744 GG genotype (but not rs3782287) was associated with lower viral load in an Asian cohort, yet surprisingly was associated with a decreased sustained virological response (SVR) rate and unfavourable therapeutic outcomes in the context of pegylated interferon plus ribavirin therapy. 19 As these studies evaluated only pegylated interferon/ribavirin therapy, it would be interesting to further evaluate potential association between treatment outcome/kinetics in the era of DAA therapy. Given that these noncoding variants are relatively prevalent in human populations (minor allele frequencies between 25% and 42%), further studies in different populations are warranted to elucidate the relationship between non-coding SR-BI variants, HCV viral load and treatment outcome.…”