Prevalence of Thymine--Adenine Dinucleotide Repeat, IL28B and IFNL4 in Thai Population and Correlation With Spontaneous Clearance and Treatment Outcome of Hepatitis C Infection

PLoS One. 2015 May 4;10(5):e0125400. doi: 10.1371/journal.pone.0125400. eCollection 2015.


Background: The interleukin-28B (IL28B) gene polymorphism is a strong baseline predictor of sustained virological response (SVR) in hepatitis C virus (HCV) treatment. The length of thymine--adenine dinucleotide repeats, or (TA)n, in the regulatory region of IL28B can affect interferon transcription. In order to determine predictive values in HCV infection, we explored the correlation among factors including (TA)n genotypes, clinical features, interferon-λ-3 (IFNL3) and interferon-λ-4 (IFNL4) polymorphisms, and HCV treatment outcome.

Methods: Sera from 492 patients with chronic HCV infection, 101 individuals with spontaneous HCV clearance and 123 healthy blood donors (control group) were analyzed. Genotyping of the (TA)n was performed by direct sequencing. The rs12979860 (IFNL3) was identified using nested PCR and sequencing, while ss469415590 (IFNL4) was identified by real-time PCR.

Results: The distribution of (TA)n was similar between individuals with spontaneous HCV clearance and chronic HCV infection, but differed significantly from healthy controls. Individuals with both (TA)n alleles ≥ 12 had significantly higher SVR rate compared to individuals with at least one (TA)n <12 allele. This strong correlation was seen for patients infected with HCV-1, HCV-3, and HCV-6. The (TA)n genotypes were not associated with HCV viral load, ALT levels and liver stiffness, but were correlated with platelet counts (p<0.001). In contrast, rs12979860 (CC) and ss469415590 (TT/TT) genotypes were associated with higher SVR rated only in patients with HCV-1.

Conclusions: The (TA)n genotypes were not associated with spontaneous clearance of HCV infection but associated with treatment response in patients infected with HCV-1, HCV-3 and HCV-6. In contrast, IFNL3 and IFNL4 polymorphisms were predictive of treatment outcome only for patients infected with HCV-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine
  • Adult
  • Alleles
  • Antiviral Agents / therapeutic use
  • Asian Continental Ancestry Group / genetics*
  • Case-Control Studies
  • Dinucleotide Repeats*
  • Female
  • Gene Frequency
  • Genotype
  • Hepacivirus* / genetics
  • Hepatitis C / drug therapy
  • Hepatitis C / genetics*
  • Hepatitis C / virology
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferons
  • Interleukins / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Polymorphism, Single Nucleotide
  • Thailand
  • Thymine
  • Treatment Outcome
  • Viral Load


  • Antiviral Agents
  • IFNL3 protein, human
  • IFNL4 protein, human
  • Interleukins
  • Interferons
  • Adenine
  • Thymine

Grant support

This work was supported by grants WCU007-HR-57 and WCU001-HR-57 from the National Research University Project, Office of Higher Education Commission, the Research Chair Grant from NSTDA, CU56-HR01 from Chulalongkorn University Centenary Academic Development Project, RES560530093 and RES560530155 from the Ratchadaphiseksomphot Endowment Fund of Chulalongkorn University, DPG5480002 from the Outstanding Professor of the Thailand Research Fund, The Graduate Scholarship for Neighboring Countries of Chulalongkorn University, SCG and MK Restaurant Company Limited. This research was also supported by Ratchadaphiseksomphot Endowment Fund for a postdoctoral fellowship, Chulalongkorn University, to Rujipat Wasitthankasem. The authors also received funding from SCG and MK Restaurant Company Limited. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.