The impact of IL-6 and IL-28B gene polymorphisms on treatment outcome of chronic hepatitis C infection among intravenous drug users in Croatia

Abstract

BackgroundSeveral genes and their single nucleotide polymorphisms (SNPs) are associated with either spontaneous resolution of hepatitis C infection or better treatment-induced viral clearance. We tested a cohort of intravenous drug users (IVDU) diagnosed with chronic hepatitis C virus (HCV) for treatment response and its association with the SNPs in the interleukin-6 (rs1800795-IL6) and the interleukin-28B (rs12979860-IL28B) genes.MethodsThe study included 110 Croatian IVDU positive for anti-HCV antibody. Genotyping was performed by polymerase chain reaction (PCR) based approach. Patients were treated by standard pegylated-interferon/ribavirin and followed throughout a period of four years, during which sustained virological response (SVR) was determined. All data were analysed with statistical package SPSS 19.0 (IBM Corp, Armonk, NY, USA) and PLINK v1.07 software.ResultsPatients showed a significantly better response to treatment according to the number of copies of the C allele carried at rs1800795-IL6 (P = 0.034). All but one of the patients with CC genotype achieved SVR (93%), whereas the response rate of patients with GG genotype was 64%. The association of rs1800795-IL6 with SVR status remained significant after further adjustment for patients’ age, fibrosis staging, and viral genotype (OR 2.15, 95% CI 1.16–4.68, P = 0.019). Distributions of allele frequencies at the locus rs12979860-IL28B among the study cohort and the underlying general population were suggestive of a protective effect of CC genotype in acquiring chronic hepatitis C in the Croatian IVDU population.DiscussionThe rs1800795-IL6 polymorphism is associated with positive response to treatment in IVDU patients positive for HCV infection. A protective role of rs12979860-IL28B CC genotype in acquiring chronic hepatitis C is suggested for Croatian IVDU population.

Evaluation of the relationship between IL-6 gene single nucleotide polymorphisms and the severity of COVID-19 in an Iranian population

“…In contrast, a study showed that the GG genotype of the rs1800795 −174 G/C polymorphism is associated with high serum levels of IL-6 and the likelihood of sustained virologic response (SVR) in patients co-infected with HCV and HIV [48] . Similarly, other studies have demonstrated that the CC genotype of the rs1800795 −174 G/C polymorphism is associated with low production of IL-6 and an attenuated immune response against chronic HCV [49] , [50] . In contrast, it has also been reported that genetic polymorphisms of IL-6 in rs1800796 (-572 G > C) were not associated with HCV infection and development of hepatocellular carcinoma (HCC) in an Egyptian population [51] .…”

Genetic and epigenetic factors associated with increased severity of Covid‐19

“…Low‐producing or high‐producing IL‐6 polymorphisms were related clearance of viral infection, sustained virologic response, and attenuated adaptive immune response (Barrett et al, 2001; Bogdanović et al, 2016; Nattermann et al, 2007). A recent meta‐analysis showed that mean IL‐6 concentrations were dramatically increased in patients with cytokine release syndrome, sepsis, and acute respiratory distress syndrome unrelated to Covid‐19 (Leisman et al, 2020).…”

STAT3 signaling pathway plays importantly genetic and functional roles in HCV infection

“…IL6 was the most reported gene to be associated with HCV infected persons or HCC patients caused by chronic HCV infection. SNP rs1800795 was associated with treatment of HCV patients infected by drug injection in Croatian (Bogdanovic et al, ). Moreover, the polymorphisms of the IL6 gene were reported to influence the histologic progression and clinical outcomes of HCV patients (Falleti et al, ; Sghaier et al, ).…”