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Interleukin 28B polymorphisms as predictor of response in hepatitis C virus genotype 2 and 3 infected patients.

ABSTRACT: Single nucleotide polymorphisms near the interleukin 28B (IL-28B) gene have been identified as strong predictors of both spontaneous or Peg-interferon (Peg-IFN) and ribavirin (RBV) induced clearance of hepatitis C virus (HCV). Several studies have shown that, in patients with genotype 1 (GT-1), rs12979860 C/C and rs8099917 T/T substitutions are associated with a more than twofold increase in sustained virological response rate to Peg-IFN and RBV treatment. Although new treatment regimens based on combination of DAA with or without IFN are in the approval phase, until combination regimens with a backbone of Peg-IFN will be used, we can expect that IL28B holds its importance. The clinical relevance of IL28B genotyping in treatment of patients infected with HCV genotype 2 (GT-2) and 3 (GT-3) remains controversial. Therefore, after a careful examination of the available literature, we analyzed the impact of IL28B in GT-2 and -3. Simple size of the studies and GT-2 and GT-3 proportion were discussed. An algorithm for the practical use of IL28B in these patients was suggested at the aim of optimizing treatment.

SUBMITTER: Mangia A

PROVIDER: S-EPMC3870545 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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Interleukin 28B polymorphisms as predictor of response in hepatitis C virus genotype 2 and 3 infected patients.

Mangia Alessandra A Mottola Leonardo L Santoro Rosanna R

World journal of gastroenterology 20131201 47

Single nucleotide polymorphisms near the interleukin 28B (IL-28B) gene have been identified as strong predictors of both spontaneous or Peg-interferon (Peg-IFN) and ribavirin (RBV) induced clearance of hepatitis C virus (HCV). Several studies have shown that, in patients with genotype 1 (GT-1), rs12979860 C/C and rs8099917 T/T substitutions are associated with a more than twofold increase in sustained virological response rate to Peg-IFN and RBV treatment. Although new treatment regimens based o ...[more]

PMID: 24379617

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Project description:IntroductionRecent studies have demonstrated the role of the interleukin 28B (IL28B) polymorphisms in predicting treatment induced and spontaneous clearance from Hepatitis C virus (HCV) infection, suggesting the possibility of tailored therapy in HCV infected patients. Genome-wide association studies have shown that single nucleotide polymorphisms (SNPs) near IL 28B gene on chromosome 19 are strong predictors of sustained virologic response (SVR) to pegylated interferon and ribavirin. This study was aimed at analyzing the co-prevalence of two common and clinically significant SNPs in a cohort of Ligurian patients.MethodsTwo SNPs (rs12979860, rs8099917) were genotyped in the IL28B locus from 175 DNA samples collected from HCV-infected consecutive patients in a Laboratory of Liguria Region, northern Italy. A real-time polymerase chain reaction in a Corbett Research Termocycler (Rotor Gene 3000A) by fluorescent probes (Fast Set IL 28B, Arrow Diagnostics) was used for the detection, according to the manufacturer's instructions.ResultsCarriers of rs12979860CT genotype predominated (87/175, 50%), homozygotes for allele C were 68/175 (39%) and the remaining were homozygotes for IFN-resistant allele T (11%). As for the rs8099917 SNP, genotypes were thus distributed: 96/175 (55%) carried the rs8099917 TT genotype, whereas 70/175 (40%) and 9/175 (5%), were heterozygotes or homozygotes for the G allele. The variants rs12979860CC and rs8099917TT were found in 39% and 54% of overall patients with HCV genotype 1, respectively. The combined assessment of examined SNPs resulted in three most prevalent genotypes (rs12979860CC/rs8099917TT, rs12979860CT/rs8099917TG and rs12979860CT/rs8099917TT) with a frequency of 35%, 31% and 18%, respectively.DiscussionRecent findings demonstrated that in carriers of rs12979860CT the determination of additional genotype of rs8099917 SNP could significantly improve the prediction of SVR. In our study cohort carriers of rs12979860CT represented 50% of all patients, who could take advantage with respect to SVR prediction by further determination of the rs8099917 SNP. The simultaneous genotyping of two IL28B SNPs should thus be recommended in HCV infected patients prior to treatment initiation.

Project description:AimTo analyze the role of rs12979860 and rs8099917 polymorphisms in hepatitis C virus (HCV) genotype 1 infection of Brazilians.MethodsA 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.ResultsSNP 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).ConclusionThe 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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Interleukin 28B polymorphisms as predictor of response in hepatitis C virus genotype 2 and 3 infected patients.

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Interleukin 28B polymorphisms as predictor of response in hepatitis C virus genotype 2 and 3 infected patients.

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