IFIT1polymorphisms predict interferon-α treatment efficiency for hepatitis B virus infection

Abstract

AIMTo investigate the association between interferon-induced protein with tetratricopeptide repeats 1 (IFIT1) polymorphisms and interferon-α (IFNα) treatment efficiency among Chinese hepatitis B virus (HBV) infection patients.METHODSTwo hundred and twenty five newly diagnosed chronic hepatitis B (CHB) patients were enrolled in the study. All of these patients received IFNα treatment for a course of 48 wk, and were followed up for 24 wk after the treatment was end. Clinical information about virological response, hepatitis B e antigen (HBeAg) seroconversion rate and combined response at the end of the treatment, as well as the sustained response by the time of following up 24 wk after the treatment, was collected. Four tag-single nucleotide polymorphisms (SNPs) of IFIT1 were selected and assessed for their association with these clinical outcomes.RESULTSAt the end of the treatment, HBeAg seroconversion was observed in 27.1% patients. Thirty-six point nine percent patients achieved virological response, and 15.6% patients exhibited combined response. Sustained response was obtained in 26.2% patients. The main HBV genotype of the study was genotype B. Patients who infected with HBV genotype B or C showed better treatment efficiency, no matter which clinical outcome was considered. Among the four SNPs assessed, rs303218 (A > G) was found to be significantly associated with the end point virological response when assuming additive model [OR = 0.64 (95%CI: 0.42-0.96), P = 0.032]. Patients who carried rs303218 GG genotype had a rather higher rate of achieving virological response (response rate: 52%, OR = 0.40, 95%CI: 0.18-0.91; P = 0.028) when compared to those had AA genotype (response rate: 27%). The most significant interaction was observed in patients who had relative lower baseline aspartate transaminase. No association between SNPs and HBeAg seroconversion, combined response or sustained response was observed.CONCLUSIONIFIT1 involves in the regulation of IFNα treatment for CHB and its polymorphism rs303218 can predict the end point virological response. The finding requires further validation.

A Missense Variant in Granulysin is Associated with the Efficacy of Pegylated-Interferon-Alpha Therapy in Chinese Patients with HBeAg-Positive Chronic Hepatitis B

“…Currently, predictive models of the efficacy for initial treatment with PegIFN were mainly reported on studies of some clinical baseline indicators 34 or SNPs. 32 , 33 , 35 Therefore, we compared the performance of clinical variables combined with PGS and that of clinical variables only, in predicting PegIFNα efficacy. The results demonstrated that the performance of the model including clinical variables combined with PGS in predicting PegIFNα efficacy was remarkably improved compared to that of the model including clinical variables only.…”

Pharmacogenomics of genetic polymorphism within the genes responsible for SARS‐CoV‐2 susceptibility and the drug‐metabolising genes used in treatment

“…82 The genotype rs303218 GG has a greater virological response rate (52%) when compared with the rs303218 GG genotype (27%). 82 Moreover, a study investigated the effect of the polymorphisms found in the 2′-5′-oligoadenylate synthetase 1 (OAS1), 2 (OAS2), 3 (OAS3) and like (OASL) on the clinical outcomes of children with chronic hepatitis B who were being treated with α-interferon. The results showed a low level of responsiveness to α-interferon in the OAS1 rs3177979G, OAS2 rs1293747T, OAS3 rs4767043G and OASL rs10849829A genotypes.…”

“…Genetic variations in different genes can affect the response to α‐interferon. For example, an SNP (rs303218) found in the interferon‐induced protein with tetratricopeptide repeats 1 (IFIT1) can affect the α‐interferon response in hepatitis B patients 82 . The genotype rs303218 GG has a greater virological response rate (52%) when compared with the rs303218 GG genotype (27%) 82 .…”

“…For example, an SNP (rs303218) found in the interferon‐induced protein with tetratricopeptide repeats 1 (IFIT1) can affect the α‐interferon response in hepatitis B patients 82 . The genotype rs303218 GG has a greater virological response rate (52%) when compared with the rs303218 GG genotype (27%) 82 . Moreover, a study investigated the effect of the polymorphisms found in the 2′‐5′‐oligoadenylate synthetase 1 (OAS1), 2 (OAS2), 3 (OAS3) and like (OASL) on the clinical outcomes of children with chronic hepatitis B who were being treated with α‐interferon.…”

Inhibiting cell-to-cell transmission to reach HDV cure: The importance of IFN-α

“…In chronic HBV-infected patients, correlations between the response to IFN treatment and single nucleotide polymorphisms within the coding sequence of ISGs have been reported, including IFIT1. 19 Genome-wide association studies, analyzing the association between gene polymorphisms and treatment responses in chronically HDV-infected patients might therefore be another step toward the identification of effector genes specifically targeting HDV, and notably preventing cell-tocell spreading.…”