title: Prenatal and early-life exposures alter expression of innate immunity genes: the PASTURE cohort study.
abstract: BACKGROUND
  There is evidence that gene expression of innate immunity receptors is upregulated by farming-related exposures.
  
  
  OBJECTIVE
  We sought to determine environmental and nutritional exposures associated with the gene expression of innate immunity receptors during pregnancy and the first year of a child's life.
  
  
  METHODS
  For the Protection Against Allergy: Study in Rural Environments (PASTURE) birth cohort study, 1133 pregnant women were recruited in rural areas of Austria, Finland, France, Germany, and Switzerland. mRNA expression of the Toll-like receptor (TLR) 1 through TLR9 and CD14 was assessed in blood samples at birth (n= 938) and year 1 (n= 752). Environmental exposures, as assessed by using questionnaires and a diary kept during year 1, and polymorphisms in innate receptor genes were related to gene expression of innate immunity receptors by using ANOVA and multivariate regression analysis.
  
  
  RESULTS
  Gene expression of innate immunity receptors in cord blood was overall higher in neonates of farmers (P for multifactorial multivariate ANOVA= .041), significantly so for TLR7 (adjusted geometric means ratio [aGMR], 1.15; 95% CI, 1.02-1.30) and TLR8 (aGMR, 1.15; 95% CI, 1.04-1.26). Unboiled farm milk consumption during the first year of life showed the strongest association with mRNA expression at year 1, taking the diversity of other foods introduced during that period into account: TLR4 (aGMR, 1.22; 95% CI, 1.03-1.45), TLR5 (aGMR, 1.19; 95% CI, 1.01-1.41), and TLR6 (aGMR, 1.20; 95% CI, 1.04-1.38). A previously described modification of the association between farm milk consumption and CD14 gene expression by the single nucleotide polymorphism CD14/C-1721T was not found.
  
  
  CONCLUSIONS
  Farming-related exposures, such as raw farm milk consumption, that were previously reported to decrease the risk for allergic outcomes were associated with a change in gene expression of innate immunity receptors in early life.
authors: Swiss Tropical and Public Health Institute, Basel, Switzerland. georg.loss@unibas.ch
authors: Georg
authors: G
authors: Loss
authors: Sondhja
authors: S
authors: Bitter
authors: Johanna
authors: J
authors: Wohlgensinger
authors: Remo
authors: R
authors: Frei
authors: Caroline
authors: C
authors: Roduit
authors: Jon
authors: J
authors: Genuneit
authors: Juha
authors: J
authors: Pekkanen
authors: Marjut
authors: M
authors: Roponen
authors: Maija-Riitta
authors: MR
authors: Hirvonen
authors: Jean-Charles
authors: JC
authors: Dalphin
authors: Marie-Laure
authors: ML
authors: Dalphin
authors: Josef
authors: J
authors: Riedler
authors: Erika
authors: E
authors: von Mutius
authors: Juliane
authors: J
authors: Weber
authors: Michael
authors: M
authors: Kabesch
authors: Sven
authors: S
authors: Michel
authors: Charlotte
authors: C
authors: Braun-Fahrländer
authors: Roger
authors: R
authors: Lauener
mesh_terms: D000328:Adult; D000383:Agriculture; D000818:Animals; D002415:Cats; D005260:Female; D005312:Fetal Blood / Q000737:chemistry / Q000276:immunology; D015870:Gene Expression / Q000276:immunology*; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D007113:Immunity, Innate / Q000235:genetics* / Q000276:immunology; D007223:Infant; D018950:Lipopolysaccharide Receptors / Q000235:genetics* / Q000276:immunology; D008297:Male; D018811:Maternal Exposure; D008892:Milk / Q000276:immunology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics* / Q000276:immunology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics* / Q000276:immunology / Q000517:prevention & control; D011446:Prospective Studies; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology; D012424:Rural Population; D011795:Surveys and Questionnaires; D051193:Toll-Like Receptors / Q000235:genetics* / Q000276:immunology
chemical_list: D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D051193:Toll-Like Receptors