Association of gene polymorphisms of pattern-recognition receptor signaling pathway with the risk and severity of hand, foot, and mouth disease caused by enterovirus 71 in Chinese Han population

J Med Virol. 2018 Apr;90(4):692-698. doi: 10.1002/jmv.25000. Epub 2018 Jan 5.

Abstract

Hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) presents with a wide variety of clinical manifestations. Host immune response is a factor that influences disease susceptibility and severity. We investigated the potential association of gene polymorphisms in the pattern recognition receptor (PRR) pathway with the risk and severity of EV71 infection. A total of 180 EV71 HFMD cases (108 severe case; 72 mild cases) were enrolled. A group of 201 sex- and age-matched children was included as a control. All subjects were genotyped for the most common single-nucleotide polymorphisms (SNPs) in the PRR and the PRR signaling pathway using the SNPscan multiple SNP typing method. Binary logistic regression analysis revealed statistically significant differences in polymorphism of RIG-1 between patients and controls (rs3739674 G vs C: OR = 1.502, 95%CI: 1.120-2.014; rs9695310 G vs C: OR = 1.782, 95%CI: 1.312-2.419). Polymorphisms of RIG-1 rs3739674 (G vs C: OR = 2.047, 95%CI: 1.307-3.205) and TLR3 rs5743305 (A vs T: OR = 0.346, 95%CI: 0.212-0.566) were found to be associated with disease severity. The results indicated that RIG-1 (rs3739674 and rs9695310) polymorphisms are associated with an increased risk of EV71-induced HFMD in Chinese children, whereas RIG-1 rs3739674 and TLR3 rs5743305 polymorphisms are associated with disease severity. These findings support an important role of innate immune mechanism in EV71 infection.

Keywords: enterovirus 71; gene polymorphism; hand foot and mouth disease; pattern recognition receptors; risk factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People
  • Child
  • Child, Preschool
  • China
  • Enterovirus A, Human / immunology*
  • Female
  • Genetic Predisposition to Disease*
  • Genotyping Techniques
  • Hand, Foot and Mouth Disease / genetics*
  • Hand, Foot and Mouth Disease / pathology
  • Humans
  • Infant
  • Male
  • Polymorphism, Single Nucleotide
  • Receptors, Pattern Recognition / genetics*
  • Receptors, Retinoic Acid / genetics*
  • Risk Assessment
  • Severity of Illness Index*
  • Signal Transduction*

Substances

  • PLAAT4 protein, human
  • Receptors, Pattern Recognition
  • Receptors, Retinoic Acid