Single-Nucleotide Polymorphisms in NOD1, RIPK2, MICB, PLCE1, TNF, and IKBKE Genes Associated with Symptomatic Dengue in Children from Colombia

Viral Immunol. 2018 Nov;31(9):613-623. doi: 10.1089/vim.2018.0028. Epub 2018 Oct 22.

Abstract

Functional immunological evidence supports the impact that the host genetic variability has on the susceptibility to develop asymptomatic or symptomatic dengue infection. Children are more prone to develop severe dengue. Thus, we have evaluated possible associations between single-nucleotide polymorphisms (SNPs) located in immune genes and the development of symptomatic dengue in children from two Colombian populations with differences in genetic backgrounds and geographical features. We genotyped 15 SNPs (in 12 genes) in 298 symptomatic children and 648 healthy controls. Ancestry proportions (APs) were inferred by genotyping 29 ancestry informative markers. We observed four SNPs associated with susceptibility to develop dengue in NOD1, RIPK2, MICB, or PLCE1 genes. Conversely, we found one SNP in TNF gene and two haplotypes in the IKBKE gene associated with resistance to develop dengue. These associations were adjusted by gender, APs, and the population of origin because the association of polymorphisms may be different in admixed populations like Colombian. To our knowledge, this is the first reported association study with dengue in IKBKE, RIPK2, and NOD1 genes. We have also confirmed previously reported associations in MICB and PLCE1 genes with dengue. Overall, our results contribute to the understanding of the genetic susceptibility/resistance to develop symptomatic dengue. Nevertheless, these associations must be validated through functional analysis.

Keywords: IKBKE; MICB; NOD1; RIPK2; SNPs; dengue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Case-Control Studies
  • Child
  • Child, Preschool
  • Colombia
  • Dengue / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Histocompatibility Antigens Class I / genetics
  • Humans
  • I-kappa B Kinase / genetics*
  • Male
  • Nod1 Signaling Adaptor Protein / genetics*
  • Phosphoinositide Phospholipase C / genetics
  • Polymorphism, Single Nucleotide*
  • Receptor-Interacting Protein Serine-Threonine Kinase 2 / genetics*
  • Sex Factors
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Histocompatibility Antigens Class I
  • MICB antigen
  • NOD1 protein, human
  • Nod1 Signaling Adaptor Protein
  • TNF protein, human
  • Tumor Necrosis Factor-alpha
  • RIPK2 protein, human
  • Receptor-Interacting Protein Serine-Threonine Kinase 2
  • I-kappa B Kinase
  • IKBKE protein, human
  • Phosphoinositide Phospholipase C
  • phospholipase C epsilon