PMID- 18305139
OWN - NLM
STAT- MEDLINE
DCOM- 20080710
LR  - 20080514
IS  - 1460-2083 (Electronic)
IS  - 0964-6906 (Linking)
VI  - 17
IP  - 11
DP  - 2008 Jun 1
TI  - Biological and genetic interaction between tenascin C and neuropeptide S receptor 
      1 in allergic diseases.
PG  - 1673-82
LID - 10.1093/hmg/ddn058 [doi]
AB  - Neuropeptide S receptor 1 (NPSR1, GPRA 154, GPRA) has been verified as a 
      susceptibility gene for asthma and related phenotypes. The ligand for NPSR1, 
      Neuropeptide S (NPS), activates signalling through NPSR1 and microarray analysis 
      has identified Tenascin C (TNC) as a target gene of NPS-NPSR1 signalling. TNC has 
      previously been implicated as a risk gene for asthma. We aimed therefore to study 
      the genetic association of TNC in asthma- and allergy-related disorders as well 
      as the biological and genetic interactions between NPSR1 and TNC. Regulation of 
      TNC was investigated using NPS stimulated NPSR1 transfected cells. We genotyped 
      12 TNC SNPs in the cross-sectional PARSIFAL study (3113 children) and performed 
      single SNP association, haplotype association and TNC and NPSR1 gene-gene 
      interaction analyses. Our experimental results show NPS-dependent upregulation of 
      TNC-mRNA. The genotyping results indicate single SNP and haplotype associations 
      for several SNPs in TNC with the most significant association to 
      rhinoconjunctivitis for a haplotype, with a frequency of 29% in cases (P = 
      0.0005). In asthma and atopic sensitization significant gene-gene interactions 
      were found between TNC and NPSR1 SNPs, indicating that depending on the NPSR1 
      genotype, TNC can be associated with either an increased or a decreased risk of 
      disease. We conclude that variations in TNC modifies, not only risk for asthma, 
      but also for rhinoconjunctivitis. Furthermore, we show epistasis based on both a 
      direct suggested regulatory effect and a genetic interaction between NPSR1 and 
      TNC. These results suggest merging of previously independent pathways of 
      importance in the development of asthma- and allergy-related traits.
FAU - Orsmark-Pietras, Christina
AU  - Orsmark-Pietras C
AD  - Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, 
      Sweden.
FAU - Melen, Erik
AU  - Melen E
FAU - Vendelin, Johanna
AU  - Vendelin J
FAU - Bruce, Sara
AU  - Bruce S
FAU - Laitinen, Annika
AU  - Laitinen A
FAU - Laitinen, Lauri A
AU  - Laitinen LA
FAU - Lauener, Roger
AU  - Lauener R
FAU - Riedler, Josef
AU  - Riedler J
FAU - von Mutius, Erika
AU  - von Mutius E
FAU - Doekes, Gert
AU  - Doekes G
FAU - Wickman, Magnus
AU  - Wickman M
FAU - van Hage, Marianne
AU  - van Hage M
FAU - Pershagen, Goran
AU  - Pershagen G
FAU - Scheynius, Annika
AU  - Scheynius A
FAU - Nyberg, Fredrik
AU  - Nyberg F
FAU - Kere, Juha
AU  - Kere J
CN  - PARSIFAL Genetics Study Group
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080227
PL  - England
TA  - Hum Mol Genet
JT  - Human molecular genetics
JID - 9208958
RN  - 0 (NPSR1 protein, human)
RN  - 0 (Neuropeptides)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (Tenascin)
RN  - 0 (neuropeptide S, human)
SB  - IM
MH  - Alleles
MH  - Asthma/*genetics
MH  - Bronchi/metabolism
MH  - Cell Line
MH  - Child
MH  - Conjunctivitis, Allergic/genetics
MH  - Epistasis, Genetic
MH  - Gene Expression Regulation
MH  - Haplotypes
MH  - Humans
MH  - Hypersensitivity/*genetics
MH  - Neuropeptides/metabolism/pharmacology
MH  - Polymorphism, Single Nucleotide
MH  - RNA, Messenger/metabolism
MH  - Receptors, G-Protein-Coupled/agonists/*genetics/metabolism
MH  - Rhinitis/genetics
MH  - Tenascin/*genetics
EDAT- 2008/02/29 09:00
MHDA- 2008/07/11 09:00
CRDT- 2008/02/29 09:00
PHST- 2008/02/29 09:00 [pubmed]
PHST- 2008/07/11 09:00 [medline]
PHST- 2008/02/29 09:00 [entrez]
AID - ddn058 [pii]
AID - 10.1093/hmg/ddn058 [doi]
PST - ppublish
SO  - Hum Mol Genet. 2008 Jun 1;17(11):1673-82. doi: 10.1093/hmg/ddn058. Epub 2008 Feb 
      27.