Article Text

This article has a correction. Please see:

PDF

10
HOMOZYGOSITY FOR HLA-C2 ALLELES IS NEGATIVELY ASSOCIATED WITH TREATMENT RESPONSE WITH PEGLYATED INTERFERON-γ AND RIBAVIRIN IN HEPATITIS C GENOTYPE 1 INFECTED INDIVIDUALS
  1. M Collison1,
  2. J L Chin2,
  3. A Abu Shanab2,
  4. R MacNicholas2,
  5. J Connell1,
  6. M Carr1,
  7. W Hall1,
  8. P A McCormick2
  1. 1 National Virus Reference Laboratory, University College Dublin, Belfield, Dublin 4, Ireland
  2. 2 Liver Unit, St Vincent's University Hospital, Dublin 4, Ireland

Abstract

Introduction Standard therapy for chronic hepatitis C virus (HCV) infection consists of pegylated interferon-? and ribavirin. This treatment is only effective in 40-50% of patients with HCV genotype 1 (G1) infections. The IL28B single nucleotide polymorphism (SNP) is well described but other host genetic factors may influence treatment response.

Aims/Background This study investigated associations between host genetic variation and treatment response to standard therapy in HCV genotype 1 and 3 (G3) infected patients. The genetic markers investigated comprised four IL28B SNPs (G1 n=89; G3 n=82): rs12979860, rs8099917, rs4803221, rs7248668; and HLA-C alleles (G1 n=71; G3 n=67): C1/C1, C1/C2 or C2/C2.

Method Nucleic acids were extracted from serum and plasma and SNP typing was performed by allelic discrimination real-time PCR, PCR-SSP and sequencing approaches.

Results For HCV genotype 1 infections, the IL28B SNP rs12979860 was the most significant genetic marker for predicting non-response to treatment, with a positive predictive value of 81.3% in patients homozygous for the T allele. HLA-C2 homozygosity was found to be significantly associated with non-response in genotype 1 infections (p=0.023). 19% (7/37) of non-responders were HLA-C2/C2 homozygoytes compared to no patients (0/34) with this genotype who achieved SVR. All HCV genotype 1 patients homozygous for HLA-C2, who did not achieve SVR, were rs12979860 heterozygotes (C/T). For HCV genotype 3 patients, no significant association was observed between HLA-C and non-response to treatment (p=0.09).

Table 1

Predictive values of the IL28B genetic variants in HCV genotype 1 and HCV genotype 3-infected individuals receiving standard therapy.

Table 2

HLA-C type of HCV genotype 1 and 3 responders and non-responders

Prediction measures were calculated using non-response as the outcome of interest, and each genetic variant as the “test” for non-response. The * notation refers to all genotypes containing that allele.

Figure 1

Frequency of HLA-C1/C2 in HCV genotype 1 and 3 responders versus non-responders.

Conclusion A combination of IL28B rs12979860 and HLA-C host genotype may better predict treatment outcomes to standard therapy for HCV genotype 1 infections.

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

Linked Articles

  • Corrections
    BMJ Publishing Group Ltd and British Society of Gastroenterology