title: Analysis of neuropeptide S receptor gene (NPSR1) polymorphism in rheumatoid arthritis.
abstract: BACKGROUND
  Polymorphism in the neuropeptide S receptor gene NPSR1 is associated with asthma and inflammatory bowel disease. NPSR1 is expressed in the brain, where it modulates anxiety and responses to stress, but also in other tissues and cell types including lymphocytes, the lungs, and the intestine, where it appears to be up-regulated in inflammation. We sought to determine whether genetic variability at the NPSR1 locus influences the susceptibility and clinical manifestation of rheumatoid arthritis (RA).
  
  
  RESULTS
  From the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) case-control study, 1,888 rheumatoid arthritis patients and 888 controls were genotyped for 19 single-nucleotide polymorphisms (SNPs) spanning the entire NPSR1 gene and 220 KB of DNA on chromosome 7p14. The association between individual genetic markers and their haplotypic combinations, respectively, and diagnosis of RA, presence of autoantibodies to citrullinated proteins (ACPA), and disease activity score based on 28 joints (DAS28) was tested. There was no association between diagnosis of RA and NPSR1 variants. However, several associations of nominal significance were detected concerning susceptibility to ACPA-negative RA and disease activity measures (DAS28). Among these, the association of SNP rs324987 with ACPA-negative RA [(p=0.004, OR=0.674 (95% CI 0.512-0.888)] and that of SNP rs10263447 with DAS28 [p=0.0002, OR=0.380 (95% CI 0.227-0.635)] remained significant after correction for multiple comparisons.
  
  
  CONCLUSIONS
  NPSR1 polymorphism may be relevant to RA susceptibility and its clinical manifestation. Specific alleles at the NPSR1 locus may represent common risk factors for chronic inflammatory diseases, including RA.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mauro
authors.initials: M
authors.lastname: D'Amato
authors.forename: Marco
authors.initials: M
authors.lastname: Zucchelli
authors.forename: Maria
authors.initials: M
authors.lastname: Seddighzadeh
authors.forename: Francesca
authors.initials: F
authors.lastname: Anedda
authors.forename: Staffan
authors.initials: S
authors.lastname: Lindblad
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Leonid
authors.initials: L
authors.lastname: Padyukov
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
chemical_list: C484532:NPSR1 protein, human; D043562:Receptors, G-Protein-Coupled