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Interleukin 28B-related polymorphisms: a pathway for understanding hepatitis C virus infection?
Raquel Francine Liermann Garcia1, Simone Moreira, Ana Lucia de Araújo Ramos
1Raquel Francine Liermann Garcia, Simone Moreira, Leslie Ecker Ferreira, Christian Evangelista Garcia, Mauro de Souza Leite Pinho, Paulo Henrique Condeixa de França, Departamento de Medicina, Universidade da Região de Joinville/Univille, Joinville, 89219-719 Santa Catarina, Brazil.
Insights
Polymorphisms in the IL28B gene, specifically rs12979860 and rs8099917, were analyzed in Brazilian patients with hepatitis C virus (HCV) genotype 1. The rs12979860 C allele and rs8099917 T allele showed a potential protective role against HCV infection and predicted treatment response.
Area of Science:
- Genetics
- Hepatology
- Virology
Background:
- Hepatitis C virus (HCV) infection is a significant global health concern.
- Interleukin-28B (IL28B) gene polymorphisms have been linked to HCV infection outcomes.
- Understanding genetic factors influencing HCV infection in diverse populations is crucial.
Purpose of the Study:
- To investigate the association of IL28B gene single nucleotide polymorphisms (SNPs), rs12979860 and rs8099917, with HCV genotype 1 infection in a Brazilian cohort.
- To determine if these SNPs predict sustained virological response (SVR) to antiviral therapy.
Main Methods:
- Genotyping of rs12979860 and rs8099917 was performed on 145 Brazilian patients with chronic hepatitis C (CHC) genotype 1 and 199 healthy controls.
- Patients received pegylated-interferon and ribavirin combination therapy.
- Polymerase chain reaction-restriction fragment length polymorphism and amplicon sequencing were used for SNP analysis.
Main Results:
- Significant differences in genotype and allele distributions of both SNPs were observed between CHC patients and controls.
- The rs12979860 C allele and CC genotype were associated with higher rates of SVR (P=0.02).
- Carriers of the rs8099917 T allele also showed significantly higher SVR rates (P=0.02).
Conclusions:
- The rs12979860 C and rs8099917 T alleles may confer a protective effect against HCV infection in Brazilians.
- These IL28B polymorphisms are potential predictors of treatment response in HCV genotype 1 patients.
Aim:
To analyze the role of rs12979860 and rs8099917 polymorphisms in hepatitis C virus (HCV) genotype 1 infection of Brazilians.
Methods:
A total of 145 adult patients diagnosed with genotype 1 chronic hepatitis C (CHC) who had completed a 48-wk regimen of pegylated-interferon α-2a or -2b plus ribavirin combination therapy were recruited from six large urban healthcare centers and 199 healthy blood donors (controls) from a single site between January 2010 and January 2012. Data on the patients' response to treatment was collected. Polymerase chain reaction-restriction fragment length polymorphism genotyping of the interleukin (IL)28B gene fragment encompassing the single nucleotide polymorphisms (SNPs) rs12979860 (C/T) and rs8099917 (T/G) was carried out for 79 of the CHC patients and 199 of the controls. Bi-directional amplicon sequencing of the two SNPs was carried out for the remaining 66 CHC patients.
Results:
SNP rs12979860 genotyping was successful in 99.5% of the controls and 97.2% of the CHC patients, whereas the SNP rs8099917 genotyping was successful in 95.5% of the controls and 100% of the CHC patients. The genotype and allele distributions for both rs12979860 and rs8099917 were significantly different between the control and CHC patient groups, with significantly higher genotype frequencies of CC and TT in the controls (P = 0.037 and 0.046, respectively) and of TT and GG in the CHC patients (P = 0.0009 and 0.0001, respectively). Analysis of the CHC patients who achieved sustained virological response (SVR) to treatment (n = 55) indicated that the rs12979860 C allele and CC genotype were predictors of SVR (P = 0.02). No significant correlation was found between rs8099917 genotypes and treatment response, but carriers of the T allele showed significantly higher rates of SVR (P = 0.02). Linkage disequilibrium analysis of the group that achieved SVR showed a significant association between rs12979860 and rs8099917 (P = 0.07).
Conclusion:
The higher allele frequency of rs12979860 C and rs8099917 T observed in non-HCV-infected individuals may indicate a potential protective role for these IL28B-related polymorphisms.
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