Association of HLA-DQ and IFNL4 polymorphisms with susceptibility to hepatitis B virus infection and clearance

Ann Hepatol. 2016 Jul-Aug;15(4):532-9.

Abstract

Background and aim. Leukocyte antigen DQ (HLA-DQ) and interferon-λ4 (IFNL4) gene polymorphisms were associated with susceptibility to chronic hepatitis B and C virus infection. This study further confirmed that variants of these genes were associated with susceptibility and spontaneous clearance of HBV infection in a Chinese population.

Material and methods: A total of 1,069 subjects were recruited and divided into three groups i.e. 397 with CLD (HBV-related chronic liver disease), 434 with SC (spontaneous clearance), and 238 HC (healthy controls). HLA-DQrs9275319 and IFNL4rs368234815, rs12971396, rs12979860, and rs8099917SNPs were genotyped using the Sequenom MassARRAY MALDI-TOF system.

Results: HLA-DQ rs9275319 showed a significant association with HBV infection (allele model, OR, 0.514; 95% CI, 0.359-0.738, adjusted p = 0.0003) and with natural clearance (allele model, OR, 1.659; 95% CI, 1.197-2.300, adjusted. However, there was no association between IFNL4 polymorphism and HBV susceptibility or natural clearance (all p > 0.05). The multifactor dimensionality reduction (MDR) test with permutation correction showed that a three-way interaction between IFNL4 and HLA-DQ SNPs was identified for HBV susceptibility (permutation p = 0.009 for the best factor model) and clearance (permutation p = 0.014 for the best factor model).

Conclusions: The data from the current study provided additional evidence for an SNP-SNP interaction between HLA-DQ and IFNL4 in regulation to HBV infection and natural clearance.

MeSH terms

  • Adult
  • Aged
  • Asian People / genetics*
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • HLA-DQ Antigens / genetics*
  • Hepatitis B / genetics
  • Hepatitis B, Chronic / genetics*
  • Humans
  • Interleukins / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Substances

  • HLA-DQ Antigens
  • IFNL4 protein, human
  • Interleukins