title: Association of Single-Nucleotide Polymorphisms in IL28B, but Not TNF-α, With Severity of Disease Caused by Andes Virus.
abstract: BACKGROUND
  Andes virus (ANDV) is the sole etiologic agent of hantavirus cardiopulmonary syndrome (HCPS) in Chile, with a fatality rate of about 35%. Individual host factors affecting ANDV infection outcome are poorly understood. In this case-control genetic association analysis, we explored the link between single-nucleotide polymorphisms (SNPs) rs12979860, rs8099917 and rs1800629 and the clinical outcome of ANDV-induced disease. The SNPs rs12979860 and rs8099917 are known to play a role in the differential expression of the interleukin 28B gene (IL28B), whereas SNP rs1800629 is implicated in the expression of tumor necrosis factor α gene (TNF-α).
  
  
  METHODS
  A total of 238 samples from confirmed ANDV-infected patients collected between 2006 and 2014, and categorized according to the severity of the disease, were genotyped for SNPs rs12979860, rs8099917, and rs1800629.
  
  
  RESULTS
  Analysis of IL28B SNPs rs12979860 and rs8099917 revealed a link between homozygosity of the minor alleles (TT and GG, respectively), displaying a mild disease progression, whereas heterozygosity or homozygosity for the major alleles (CT/CC and TG/TT, respectively) in both IL28B SNPs is associated with severe disease. No association with the clinical outcome of HCPS was observed for TNF-α SNP rs1800629 (TNF -308G>A).
  
  
  CONCLUSIONS
  The IL28B SNPs rs12979860 and rs8099917, but not TNF-α SNP rs1800629, are associated with the clinical outcome of ANDV-induced disease, suggesting a possible link between IL28B expression and ANDV pathogenesis.
authors.affiliation: Laboratorio de Virología Molecular, Instituto Milenio de Inmunología e Inmunoterapia.
authors.forename: Jenniffer
authors.initials: J
authors.lastname: Angulo
authors.affiliation: Laboratorio de Virología Molecular, Instituto Milenio de Inmunología e Inmunoterapia.
authors.forename: Karla
authors.initials: K
authors.lastname: Pino
authors.affiliation: Laboratorio de Virología Molecular, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay.
authors.forename: Natalia
authors.initials: N
authors.lastname: Echeverría-Chagas
authors.affiliation: Laboratorio de Infectología, Centro de Investigaciones Médicas, Escuela de Medicina, División de Pediatría.
authors.forename: Claudia
authors.initials: C
authors.lastname: Marco
authors.affiliation: Laboratorio de Infectología, Centro de Investigaciones Médicas, Escuela de Medicina, División de Pediatría.
authors.forename: Constanza
authors.initials: C
authors.lastname: Martínez-Valdebenito
authors.affiliation: Subdepartamento de Virología Clínica, Departamento Laboratorio Biomédico Nacional y de Referencia.
authors.forename: Héctor
authors.initials: H
authors.lastname: Galeno
authors.affiliation: Subdepartamento de Virología Clínica, Departamento Laboratorio Biomédico Nacional y de Referencia.
authors.forename: Eliecer
authors.initials: E
authors.lastname: Villagra
authors.affiliation: Subdepartamento de Virología Clínica, Departamento Laboratorio Biomédico Nacional y de Referencia.
authors.forename: Lilian
authors.initials: L
authors.lastname: Vera
authors.affiliation: Subdepartamento de Virología Clínica, Departamento Laboratorio Biomédico Nacional y de Referencia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Lagos
authors.affiliation: Subdepartamento de Virología Clínica, Departamento Laboratorio Biomédico Nacional y de Referencia.
authors.forename: Natalia
authors.initials: N
authors.lastname: Becerra
authors.affiliation: Subdepartamento de Virología Clínica, Departamento Laboratorio Biomédico Nacional y de Referencia.
authors.forename: Judith
authors.initials: J
authors.lastname: Mora
authors.affiliation: Departamento de Asuntos Científicos, Instituto de Salud Pública de Chile, Santiago.
authors.forename: Andrea
authors.initials: A
authors.lastname: Bermúdez
authors.affiliation: Departamento de Asuntos Científicos, Instituto de Salud Pública de Chile, Santiago.
authors.forename: Marcela
authors.initials: M
authors.lastname: Cárcamo
authors.affiliation: Departamento de Asuntos Científicos, Instituto de Salud Pública de Chile, Santiago.
authors.forename: Janepsy
authors.initials: J
authors.lastname: Díaz
authors.affiliation: Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile.
authors.forename: Juan Francisco
authors.initials: JF
authors.lastname: Miquel
authors.affiliation: Laboratorio de Infectología, Centro de Investigaciones Médicas, Escuela de Medicina, División de Pediatría.
authors.forename: Marcela
authors.initials: M
authors.lastname: Ferrés
authors.affiliation: Laboratorio de Virología Molecular, Instituto Milenio de Inmunología e Inmunoterapia.
authors.forename: Marcelo
authors.initials: M
authors.lastname: López-Lastra
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D002677:Chile; D005260:Female; D056726:Genetic Association Studies; D060005:Genotyping Techniques; D006476:Orthohantavirus / Q000302:isolation & purification*; D018778:Hantavirus Infections / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult; D000095022:Interferon Lambda
chemical_list: D007372:Interferons; D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; C000624353:interferon-lambda, human; D000095022:Interferon Lambda
keywords: ANDV; HCPS; IL28B; SNP; TNF-alpha