title: Single nucleotide polymorphisms in immune response genes in acute Q fever cases with differences in self-reported symptoms.
abstract: Genes involved in human immune response are well recognized to influence the clinical course of infection. The association of host genetics with susceptibility to and severity of clinical symptoms in acute Q fever was investigated. Single nucleotide polymorphisms (SNPs) in the IFNG (rs2430561/rs1861493), STAT1 (rs1914408), and VDR (rs2228570) genes were determined in 85 patients from the 2007 Dutch acute Q fever outbreak, and a symptom score was calculated. IFNG rs1861493 showed a significant association with the symptom score; IFNG rs2430561 showed a similar trend. These SNPs were then used to reproduce results in a 2009 outbreak population (n = 123). The median symptom score differed significantly in both populations: 2 versus 7. The significant association of IFNG rs1861493 with symptom score in the first population was not reproduced in the second population. We hypothesize that individuals in the second outbreak were exposed to a higher Coxiella burnetii dose compared to the first, which overruled the protection conferred by the A-allele of IFNG rs1861493 in the first population.
authors.affiliation: Department of Medical Microbiology and Infection Control, Jeroen Bosch Hospital, P.O. Box 90153, 5200 ME, 's-Hertogenbosch, The Netherlands, l.wielders@jbz.nl.
authors.forename: C C H
authors.initials: CC
authors.lastname: Wielders
authors.forename: V H
authors.initials: VH
authors.lastname: Hackert
authors.forename: B
authors.initials: B
authors.lastname: Schimmer
authors.forename: H M
authors.initials: HM
authors.lastname: Hodemaekers
authors.forename: A
authors.initials: A
authors.lastname: de Klerk
authors.forename: C J P A
authors.initials: CJ
authors.lastname: Hoebe
authors.forename: P M
authors.initials: PM
authors.lastname: Schneeberger
authors.forename: Y T H P
authors.initials: YT
authors.lastname: van Duynhoven
authors.forename: R
authors.initials: R
authors.lastname: Janssen
mesh_terms: D000328:Adult; D000818:Animals; D016022:Case-Control Studies; D003381:Coxiella / Q000276:immunology*; D004196:Disease Outbreaks; D005260:Female; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D011778:Q Fever / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology / Q000473:pathology*; D018167:Receptors, Calcitriol / Q000235:genetics*; D050794:STAT1 Transcription Factor / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: C573415:IFNG protein, human; D018167:Receptors, Calcitriol; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; C579457:VDR protein, human; D007371:Interferon-gamma