A thymine-adenine dinucleotide repeat polymorphism near IL28B is associated with spontaneous clearance of hepatitis C virus

J Gastroenterol. 2015 Oct;50(10):1069-77. doi: 10.1007/s00535-015-1056-1. Epub 2015 Mar 5.

Abstract

Background: Genome-wide association studies have revealed several single-nucleotide polymorphisms around interleukin 28B (IL28B) that are strongly associated with hepatitis C virus (HCV) clearance. However, their predictive value is not perfect, which suggests that other genetic factors may also be involved in HCV clearance. We previously reported a wide variation in the length of a thymine-adenine (TA) dinucleotide repeat in the promoter region of IL28B and that the transcriptional activity of the promoter increased gradually in a TA repeat length-dependent manner.

Methods: We determined the length of the TA repeats of 1,060 Japanese and 201 African-American samples to investigate the relation to spontaneous HCV clearance.

Results: The distribution of the TA repeats greatly differed between the two ethnicities. The variation ranged from 10 to 18 repeats, and the most frequent allele, 12, accounted for over 80% for Japanese. The African-American data showed a gently sloping distribution, and the allele with six repeats was detected only in the African-American sample. The TA repeats 11 or greater were correlated with spontaneous clearance. Multiple logistic regression analysis extracted the genotype of the TA repeats as an independent factor in both the Japanese [p = 0.0004, odds ratio (OR) = 13.02 95% confidence interval (CI) = 2.59-237.0] and African-American (p = 0.027, OR = 3.70 95% CI = 1.16-11.8) populations.

Conclusions: A long TA repeat in the promoter region of IL28B was associated with spontaneous HCV clearance. Although its efficacy may be limited in Japanese population because of its allele distribution, this novel genetic factor will be useful for predicting HCV clearance especially for the African Americans.

Keywords: Genetic marker; Interferon lambda 3; Microsatellite.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine / metabolism*
  • Adolescent
  • Adult
  • Aged
  • Alleles
  • DNA, Viral / genetics*
  • Dinucleotide Repeats
  • Female
  • Gene Frequency
  • Genetic Variation
  • Genome-Wide Association Study
  • Genotype
  • Hepacivirus / genetics*
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / metabolism
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferons
  • Interleukins / genetics*
  • Interleukins / metabolism
  • Male
  • Middle Aged
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide*
  • Thymine / metabolism*
  • Young Adult

Substances

  • DNA, Viral
  • IFNL3 protein, human
  • Interleukins
  • Interferons
  • Adenine
  • Thymine