HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

A polymorphism in IL28B distinguishes exposed, uninfected individuals from spontaneous resolvers of HCV infection.

AbstractBACKGROUND & AIMS:
Polymorphisms in the interleukin-28B (IL28B) gene are associated with outcomes from infection with hepatitis C virus (HCV). However, the role of these polymorphisms in protecting injection drug users who are at high risk for HCV infection but do not have detectable antibodies against HCV or HCV RNA (exposed uninfected) has not been demonstrated. We investigated whether these individuals have the IL28B genotype rs12979860-CC, which protects some individuals against HCV infection.
METHODS:
Seventy-four exposed uninfected individuals, 89 spontaneous resolvers, and 234 chronically infected individuals were genotyped to determine single nucleotide polymorphisms at IL28B.rs12979860.
RESULTS:
Exposed, uninfected individuals had a significantly lower frequency of the protective genotype (rs12979860-CC) than anti-HCV-positive spontaneous resolvers (41.9% vs 69.7%, respectively; P=.0005; odds ratio [OR], 0.31; 95% confidence interval [CI]: 0.16-0.60) but a similar frequency to patients who were chronically infected (41.9% vs 43.6%, respectively; P=ns). However, exposed, uninfected individuals had a significantly higher frequency of homozygosity for killer cell immunoglobulin-like receptor 2DL3:group 1 HLA-C (KIR2DL3:HLA-C1) than those with chronic infection (31.1% vs 13.3%, respectively; P=.0008; OR, 2.95; 95% CI: 1.59-5.49). For patients who spontaneously resolved infection, IL28B and KIR:HLA protected, independently, against chronic HCV infection, based on logistic regression and synergy analyses (synergy factor, 1.3; 95% CI: 0.37-4.75; P synergy=.6).
CONCLUSIONS:
IL28B and KIR2DL3:HLA-C1 are independently associated with spontaneous resolution of viremia following HCV exposure. Resistance to HCV infection in exposed uninfected cases is associated with homozygosity for KIR2DL3:HLA-C1 but not the single nucleotide polymorphism IL28B.rs12979860. Uninfected individuals are therefore a distinct population from patients who spontaneously resolve HCV infection. Distinct, nonsynergistic innate immune mechanisms can determine outcomes of HCV exposure.
AuthorsSusanne Knapp, Usama Warshow, K M Alexander Ho, Doha Hegazy, Ann-Margaret Little, Andrew Fowell, Graeme Alexander, Mark Thursz, Matthew Cramp, Salim I Khakoo
JournalGastroenterology (Gastroenterology) Vol. 141 Issue 1 Pg. 320-5, 325.e1-2 (Jul 2011) ISSN: 1528-0012 [Electronic] United States
PMID21600205 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.
Chemical References
  • HLA-C Antigens
  • Hepatitis C Antibodies
  • IFNL3 protein, human
  • Interleukins
  • KIR2DL3 protein, human
  • RNA, Viral
  • Receptors, KIR2DL3
  • Interferons
Topics
  • Adult
  • Disease Progression
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • HLA-C Antigens (genetics)
  • Hepacivirus (genetics, immunology)
  • Hepatitis C (diagnosis, genetics, immunology, prevention & control)
  • Hepatitis C Antibodies (blood)
  • Hepatitis C, Chronic (diagnosis, genetics, immunology, prevention & control)
  • Humans
  • Immunity, Innate (genetics)
  • Interferons
  • Interleukins (genetics)
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Phenotype
  • Polymorphism, Single Nucleotide
  • RNA, Viral (blood)
  • Receptors, KIR2DL3 (genetics)
  • Remission, Spontaneous
  • Risk Assessment
  • Risk Factors
  • Substance Abuse, Intravenous (complications)
  • United Kingdom
  • Viral Load

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: