Neuropeptide S (NPS) variants modify the signaling and risk effects of NPS Receptor 1 (NPSR1) variants in asthma

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Acevedo , N , Ezer , S , Merid , S K , Gaertner , V D , Soderhall , C , D'Amato , M , Kabesch , M , Melen , E , Kere , J & Pulkkinen , V 2017 , ' Neuropeptide S (NPS) variants modify the signaling and risk effects of NPS Receptor 1 (NPSR1) variants in asthma ' , PLoS One , vol. 12 , no. 5 , 0176568 . https://doi.org/10.1371/journal.pone.0176568

Title: Neuropeptide S (NPS) variants modify the signaling and risk effects of NPS Receptor 1 (NPSR1) variants in asthma
Author: Acevedo, Nathalle; Ezer, Sini; Merid, Simon Kebede; Gaertner, Vincent D.; Soderhall, Cilia; D'Amato, Mauro; Kabesch, Michael; Melen, Erik; Kere, Juha; Pulkkinen, Ville
Contributor: University of Helsinki, Research Programs Unit
University of Helsinki, Research Programs Unit
University of Helsinki, Clinicum
Date: 2017-05-02
Language: eng
Number of pages: 17
Belongs to series: PLoS One
ISSN: 1932-6203
URI: http://hdl.handle.net/10138/197194
Abstract: Single nucleotide polymorphisms (SNPs) close to the gain-of-function substitution, Asn(107) Ile (rs324981, A>T), in Neuropeptide S Receptor 1 (NPSR1) have been associated with asthma. Furthermore, a functional SNP (rs4751440, G>C) in Neuropeptide S (NPS) encodes a Val(6)Leu substitution on the mature peptide that results in reduced bioactivity. We sought to examine the effects of different combinations of these NPS and NPSR1 variants on downstream signaling and genetic risk of asthma. In transfected cells, the magnitude of NPSR1-induced activation of cAMP/PKA signal transduction pathways and downstream gene expression was dependent on the combination of the NPS and NPSR1 variants with NPS-Val(6)/NPSR1-Ile(107) resulting in strongest and NPS-Leu(6)/NPSR1-Asn(107) in weakest effects, respectively. One or two copies of the NPS-Leu(6) (rs4751440) were associated with physician-diagnosed childhood asthma (OR: 0.67, 95% CI 0.49-0.92, p = 0.01) and together with two other linked NPS variants (rs1931704 and rs10830123) formed a protective haplotype (p = 0.008) in the Swedish birth cohort BAMSE (2033 children). NPS rs10830123 showed epistasis with NPSR1 rs324981 encoding Asn(107)Ile (p = 0.009) in BAMSE and with the linked NPSR1 rs17199659 (p = 0.005) in the German MAGIC/ISAAC II cohort (1454 children). In conclusion, NPS variants modify asthma risk and should be considered in genetic association studies of NPSR1 with asthma and other complex diseases.
Subject: PROTEIN-COUPLED RECEPTOR-154
GENOME-WIDE ASSOCIATION
RHEUMATOID-ARTHRITIS
GENE POLYMORPHISM
CHILDHOOD ASTHMA
PANIC DISORDER
IGE LEVELS
EXPRESSION
POPULATION
RESPONSES
3121 General medicine, internal medicine and other clinical medicine
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