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<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.
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<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: Jerzy Wegiel; Izabela Kuchna; Krzysztof Nowicki; Humi Imaki; Jarek Wegiel; Elaine Marchi; Shuang Yong Ma; Abha Chauhan; Ved Chauhan; Teresa Wierzba Bobrowicz; Mony de Leon; Leslie A Saint Louis; Ira L Cohen; Eric London; W Ted Brown; Thomas Wisniewski Journal: Acta Neuropathol Date: 2010-03-03 Impact factor: 17.088
Authors: Zongyao Wang; John S Sundy; Catherine M Foss; Huiman X Barnhart; Scott M Palmer; Sallie D Allgood; Evan Trudeau; Katie M Alexander; Marc C Levesque Journal: J Asthma Allergy Date: 2013-06-25
Authors: Christina Orsmark Pietras; Johanna Vendelin; Francesca Anedda; Sara Bruce; Mikael Adner; Lilli Sundman; Ville Pulkkinen; Harri Alenius; Mauro D'Amato; Cilla Söderhäll; Juha Kere Journal: BMC Pulm Med Date: 2011-06-27 Impact factor: 3.317
Authors: Lovisa E Reinius; Anna Gref; Annika Sääf; Nathalie Acevedo; Maaike Joerink; Maciej Kupczyk; Mauro D'Amato; Anna Bergström; Erik Melén; Annika Scheynius; Sven-Erik Dahlén; Göran Pershagen; Cilla Söderhäll; Juha Kere Journal: PLoS One Date: 2013-01-23 Impact factor: 3.240
Authors: Susanne Bornelöv; Annika Sääf; Erik Melén; Anna Bergström; Behrooz Torabi Moghadam; Ville Pulkkinen; Nathalie Acevedo; Christina Orsmark Pietras; Markus Ege; Charlotte Braun-Fahrländer; Josef Riedler; Gert Doekes; Michael Kabesch; Marianne van Hage; Juha Kere; Annika Scheynius; Cilla Söderhäll; Göran Pershagen; Jan Komorowski Journal: PLoS One Date: 2013-11-19 Impact factor: 3.240