Impact of IL28B and OAS gene family polymorphisms on interferon treatment response in Caucasian children chronically infected with hepatitis B virus

Abstract

AIMTo investigate the impact of IL28B and OAS gene polymorphisms on interferon treatment responses in children with chronic hepatitis B.METHODSWe enrolled 52 children (between the ages of 4 and 18) with hepatitis B e antigen-negative chronic hepatitis B (CHB), who were treated with pegylated interferon alfa for 48 wk. Single nucleotide polymorphisms in the OAS1 (rs1131476), OAS2 (rs1293747), OAS3 (rs2072136), OASL (rs10849829) and IL28B (rs12979860, rs12980275 and rs8099917) genes were studied to examine their associations with responses to IFN treatment in paediatric patients. We adopted two criteria for the therapeutic response, achieving an hepatitis B virus (HBV) DNA level < 2000 IU/mL and normalization of ALT activity (< 40 IU/L). To perform the analyses, we compared the patients in terms of achieving a partial response (PR) and a complete response (CR) upon measurement at the 24-wk post-treatment follow-up.RESULTSThe PR and CR rates were 80.8% and 42.3%, respectively. Factors such as age, gender and liver histology had no impact on the type of response (partial or complete). A statistically significant relationship between higher baseline HBV DNA and ALT activity levels and lower rates of PR and CR was shown (P < 0.05). The allele association analysis revealed that only the IL-28B rs12979860 (C vs T) and IL28B rs12980275 (A vs G) markers significantly affected the achievement of PR (P = 0.021, OR = 3.3, 95%CI: 1.2-9.2 and P = 0.014, OR = 3.7, 95%CI: 1.3-10.1, respectively). However, in the genotype analysis, only IL-28B rs12980275 was significantly associated with PR (AA vs AG-GG, P = 0.014, OR = 10.9, 95%CI: 1.3-93.9). The association analysis for CR showed that the TT genotype of IL28B rs12979860 was present only in the no-CR group (P = 0.033) and the AA genotype of OASL rs10849829 was significantly more frequent in the no-CR group (P = 0.044, OR = 0.26, 95%CI: 0.07-0.88). The haplotype analysis revealed significant associations between PR and CR and OAS haplotype (P = 0.0002 and P = 0.001, respectively), but no association with IL28B haplotype was observed.CONCLUSIONIL28B and OAS polymorphisms are associated with different clinical outcomes in CHB children treated with interferon.

Identified OAS3 gene variants associated with coexistence of HBsAg and anti‐HBs in chronic HBV infection

“…In humans, there are four OAS genes, all stimulated by IFN, but only three of these (OAS1, OAS2 and OAS3) encode catalytically active proteins . Genetic variants in the OAS genes are known to affect OAS activity and are associated with severity and/or outcomes of many kinds of viral infections, such as hepatitis C virus (HCV) infection,, tick‐borne encephalitis (TBE), dengue virus, enterovirus‐71, West Nile virus and HBV . In particular to hepatitis B disease, multiple viral and host factors are reported to affect host immune and antiviral responses and, thus, are associated with variable disease outcomes.…”

Influence ofIL28BandMxAgene polymorphisms on HCV clearance in Han Chinese population

“…CHC virus infection clearly posed a challenge to public health. With the development of molecular biology, more and more researches focus on the relationship between gene polymorphism and hepatitis C infection [13, 14]. The present study investigated the association of IL28B gene and MxA gene polymorphisms with HCV clearance among Chinese Han population.…”

Influence of OASL gene polymorphisms on host response to interferon therapy in chronic hepatitis C virus patients

“…Domagalski et al analyzing the influence of IL28B and OAS polymorphisms, find an association between OASL gene polymorphism (rs1083129) and response to interferon therapy in pediatric cases with Hepatitis B infection (33).…”