Significance of transporter associated with antigen processing 2 (TAP2) gene polymorphisms in susceptibility to dengue viral infection

J Clin Immunol. 2008 May;28(3):256-62. doi: 10.1007/s10875-007-9154-3.

Abstract

Background and aims: The polymorphic transporter associated with antigen processing (TAP)1 and TAP2 genes encode subunits of the transporter that delivers peptides to the human leukocyte antigen class I molecules. Because the polymorphism of the TAP genes has been shown to affect peptide transport, it has been suggested that TAP genes are potential regulators of the immune response. We recently reported that TAP1 gene polymorphism is associated with severe dengue infection. This study was carried out to elucidate whether TAP2 polymorphisms are involved in diverse pathogenesis of dengue infection.

Materials and methods: This study included 100 controls and 197 dengue-infected patients who were further categorized into 90 dengue fever (DF) cases, 75 dengue hemorrhagic fever cases (DHF), and 32 dengue shock syndrome (DSS) cases as per WHO grading system. TAP2 gene polymorphisms were determined by amplification refraction mutation system-polymerase chain reaction.

Results: The frequency of isoleucine at TAP2 379 (34.5%) was increased among DHF in comparison to controls (21%, P = 0.014). DHF cases were more likely to be heterozygous at TAP2 379 (50.7%) than controls [24%, odds ratio (OR) = 2.11, P = 0.001]. Significantly high proportion of DHF was found to have TAP2 665 threonine/alanine (THR/ALA) genotypes (30.7%) when compared with DF (13.3%, OR = 2.3, P = 0.006) cases. There was no difference in the genotypes studied between DSS and controls or DF or DHF.

Conclusion: This first report on TAP 2 gene polymorphism in dengue suggested that heterozygous pattern at TAP2 379 locus confers susceptibility to DHF, and TAP2 665 THR/ALA genotype was found to be a risk factor for development of DHF.

Publication types

  • Comparative Study

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters / genetics*
  • Adolescent
  • Adult
  • Aged
  • Amino Acid Substitution / genetics
  • Dengue Virus / immunology*
  • Female
  • Gene Frequency
  • Genetic Carrier Screening
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic*
  • Severe Dengue / genetics*
  • Severe Dengue / immunology*
  • Severe Dengue / virology

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 3
  • ATP-Binding Cassette Transporters
  • TAP2 protein, human