title: The protective effect of farm animal exposure on childhood allergy is modified by NPSR1 polymorphisms.
abstract: BACKGROUND
  Little is known about the asthma candidate gene neuropeptide S receptor 1 (NPSR1) in relation to environmental exposures, but recent evidences suggest its role as an effect modifier.
  
  
  OBJECTIVE
  To explore the interaction between NPSR1 polymorphisms and environmental exposures related to farming lifestyle and to study the in vitro effects of lipopolysaccharide (LPS) stimulation on NPSR1 expression levels.
  
  
  METHODS
  We studied 3113 children from PARSIFAL, a European cross-sectional study on environmental/lifestyle factors and childhood allergy, partly focused on children brought up on a farm. Information on exposures and outcomes was primarily obtained from parental questionnaires. Seven tagging polymorphisms were analysed in a conserved haplotype block of NPSR1. Multivariate logistic regression was used to evaluate a multiplicative model of interaction. NPSR1 protein and messenger RNA (mRNA) levels in monocytes were measured after LPS stimulation by fluorescence activated cell sorting (FACS) and quantitative real-time polymerase chain reaction (PCR).
  
  
  RESULTS
  A strong interaction was seen between current regular contact to farm animals and several NPSR1 polymorphisms, particularly rs323922 and rs324377 (p<0.005), with respect to allergic symptoms. Considering the timing of initiation of such current regular farm animal contact, significant interactions with these and two additional polymorphisms (SNP546333, rs740347) were revealed. In response to LPS, NPSR1-A protein levels in monocytes were upregulated (p = 0.002), as were NPSR1-A mRNA levels (p = 0.02).
  
  
  CONCLUSIONS
  The effect of farm animal contact on the development of allergic symptoms in children is modified by NPSR1 genetic background.
authors.affiliation: Department of Biosciences and Nutrition, Hälsovägen 7-9, 14157 Huddinge, Sweden. sara.bruce@biosci.ki.se
authors.forename: S
authors.initials: S
authors.lastname: Bruce
authors.forename: F
authors.initials: F
authors.lastname: Nyberg
authors.forename: E
authors.initials: E
authors.lastname: Melén
authors.forename: A
authors.initials: A
authors.lastname: James
authors.forename: V
authors.initials: V
authors.lastname: Pulkkinen
authors.forename: C
authors.initials: C
authors.lastname: Orsmark-Pietras
authors.forename: A
authors.initials: A
authors.lastname: Bergström
authors.forename: B
authors.initials: B
authors.lastname: Dahlén
authors.forename: M
authors.initials: M
authors.lastname: Wickman
authors.forename: E
authors.initials: E
authors.lastname: von Mutius
authors.forename: G
authors.initials: G
authors.lastname: Doekes
authors.forename: R
authors.initials: R
authors.lastname: Lauener
authors.forename: J
authors.initials: J
authors.lastname: Riedler
authors.forename: W
authors.initials: W
authors.lastname: Eder
authors.forename: M
authors.initials: M
authors.lastname: van Hage
authors.forename: G
authors.initials: G
authors.lastname: Pershagen
authors.forename: A
authors.initials: A
authors.lastname: Scheynius
authors.forename: J
authors.initials: J
authors.lastname: Kere
mesh_terms: D000293:Adolescent; D000818:Animals; D000829:Animals, Domestic; D002648:Child; D002675:Child, Preschool; D004781:Environmental Exposure; D005434:Flow Cytometry; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D009000:Monocytes / Q000378:metabolism; D015999:Multivariate Analysis; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D012130:Respiratory Hypersensitivity / Q000453:epidemiology / Q000235:genetics*
chemical_list: C484532:NPSR1 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled