The platelet derived growth factor-B polymorphism is associated with risk of severe fever with thrombocytopenia syndrome in Chinese individuals

Oncotarget. 2016 May 31;7(22):33340-9. doi: 10.18632/oncotarget.9043.

Abstract

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus named SFTS virus (SFTSV). We hypothesize that host genetic variations may contribute to susceptibility to SFTS.

Results: Compared with the rs1800818 AA genotype, AG + GG genotypes were significantly associated with increased susceptibility to SFTS (odds ratio, 1.66, 95% confidence interval = 1.28-2.16; P < 0.001). By using the ELISA assay, we observed that PDGF-BB concentration was significantly reduced in acute phase of patients than in the controls (P < 0.001) and recovered patients at 6 month (P = 0.007) and 12 month (P = 0.003). A persistently reduced PDGF-BB was also revealed from the SFTSV-infected C57BL/6J mice (P < 0.001). The rs1800818 G allele was associated with decreased serum PDGF-BB levels in SFTS patients at their early infection (P = 0.015). In accordance, the relative mRNA levels of the at-risk G allele of 1800818 were lower than those of the A allele in heterozygous cell from acute phase of SFTS patients. PDGF-B rs1800818 conferred no susceptibility to severe or fatal outcome in SFTS patients.

Materials and methods: An initially small-scale case-control association study guided the selection of platelet derived growth factor-B (PDGF-B) rs1800818 in 1020 SFTS patients and 1353 controls. Functional analyses were conducted to verify the biological significance of rs1800818 polymorphism.

Conclusions: Our findings suggest that the PDGF-B rs1800818 polymorphism might play a role in mediating the susceptibility to SFTS.

Keywords: PDGF-B; cytokines; polymorphism; severe fever with thrombocytopenia syndrome; susceptibility.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Asian People / genetics
  • Becaplermin
  • Bunyaviridae Infections / blood
  • Bunyaviridae Infections / ethnology
  • Bunyaviridae Infections / genetics*
  • Bunyaviridae Infections / virology
  • Case-Control Studies
  • China / epidemiology
  • Disease Models, Animal
  • Female
  • Fever / blood
  • Fever / ethnology
  • Fever / genetics*
  • Fever / virology
  • Gene Frequency
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Heterozygote
  • Homozygote
  • Humans
  • Male
  • Mice, Inbred C57BL
  • Middle Aged
  • Phenotype
  • Polymorphism, Single Nucleotide*
  • Proto-Oncogene Proteins c-sis / blood
  • Proto-Oncogene Proteins c-sis / genetics*
  • Risk Factors
  • Severity of Illness Index
  • Syndrome
  • Thrombocytopenia / blood
  • Thrombocytopenia / ethnology
  • Thrombocytopenia / genetics*
  • Thrombocytopenia / virology
  • Time Factors

Substances

  • Proto-Oncogene Proteins c-sis
  • Becaplermin