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Single nucleotide polymorphisms and haplotypes in the IL10 region associated with HCV clearance

T K Oleksyk1, C L Thio, A L Truelove

  • 1Laboratory of Genomic Diversity, National Cancer Institute at Frederick, Frederick, MD 21702, USA.

Genes and Immunity
|April 9, 2005
PubMed

Insights

Genetic variations in interleukin-10 (IL10) and related genes are linked to spontaneous Hepatitis C virus (HCV) clearance in African Americans. These findings highlight host genetic factors influencing viral persistence versus resolution.

Area of Science:

  • Immunogenetics
  • Virology
  • Infectious Diseases

Background:

  • Hepatitis C virus (HCV) infection often becomes chronic, but spontaneous clearance occurs in ~15% of cases.
  • Host immune responses, particularly inflammation, are critical in determining HCV infection outcomes.
  • Previous studies suggest Interleukin-10 (IL10) gene polymorphisms may influence HCV clearance and treatment success.

Purpose of the Study:

  • To investigate the association between single nucleotide polymorphisms (SNPs) in the IL10 gene region and spontaneous HCV clearance versus chronic infection.
  • To explore the role of IL10 and its paralogs (IL19, IL20, IL24) in determining HCV infection course.

Main Methods:

  • Genotyping of 54 SNPs across the IL10 region, including within the IL10 gene and its paralogs.
  • Association analysis of SNPs and reconstructed haplotypes with HCV clearance in African American and European American cohorts.
  • Comparison of genetic associations between populations with differing HCV clearance rates.

Main Results:

  • SNPs in the IL10 and IL19/IL20 regions were significantly associated with HCV clearance in African Americans (P=0.05-0.002).
  • These associations remained significant after haplotype reconstruction using the expectation-maximization algorithm.
  • No significant associations were found in the European American cohort.

Conclusions:

  • Genetic variants within the IL10 and IL19/IL20 gene regions may play a role in the natural clearance of Hepatitis C virus.
  • These genetic associations appear specific to the African-American population, suggesting population-specific host genetic factors.
  • The findings underscore the importance of host genetic background in the outcome of HCV infection.

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