The protective effect of farm animal exposure on childhood allergy is modified by NPSR1 polymorphisms

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.Objectives: 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