title: Potential association of muscarinic receptor 3 gene variants with primary Sjogren's syndrome.
abstract: BACKGROUND
  Primary Sjögren's syndrome (pSS) is characterised by a chronic inflammation of exocrine glands. Salivary gland infiltrates, however, do not correlate well with disease symptoms, and a primary role for the salivary gland parenchyma in disease development has been suggested. Specifically, dysfunction of exocrine pathways involving the muscarinic receptor 3 (CHRM3) has been indicated.
  
  
  OBJECTIVE
  To investigate possible genetic divergence in the CHRM3 gene in patients with pSS.
  
  
  METHODS
  530 patients with pSS and 532 controls from a combined Swedish and Norwegian cohort were genotyped for 84 single nucleotide polymorphisms (SNPs) distributed throughout CHRM3.
  
  
  RESULTS
  Genetic association was observed with five SNPs localised in intron 3 and 4 of CHRM3, the strongest being rs7548522 (minor allele frequency = 0.06, OR=1.93, 95% CI (1.24 to 3.01); p=0.0033). In addition, clinical parameters, including focus score, abnormal Schirmer's test and presence of autoantibodies, were associated with different SNPs in CHRM3.
  
  
  CONCLUSIONS
  The study demonstrates a novel association of CHRM3 polymorphisms with pSS, suggesting a functional role for CHRM3 and the salivary gland parenchyma in the pathogenesis of pSS.
authors: Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Norway. silke.appel@gades.uib.no
authors: Silke
authors: S
authors: Appel
authors: Stephanie
authors: S
authors: Le Hellard
authors: Ove
authors: O
authors: Bruland
authors: Johan G
authors: JG
authors: Brun
authors: Roald
authors: R
authors: Omdal
authors: Gudlaug
authors: G
authors: Kristjansdottir
authors: Elke
authors: E
authors: Theander
authors: Gunnel
authors: G
authors: Nordmark
authors: Marika
authors: M
authors: Kvarnström
authors: Per
authors: P
authors: Eriksson
authors: Lars
authors: L
authors: Rönnblom
authors: Marie
authors: M
authors: Wahren-Herlenius
authors: Roland
authors: R
authors: Jonsson
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043587:Receptor, Muscarinic M3 / Q000235:genetics*; D012859:Sjogren's Syndrome / Q000235:genetics*
chemical_list: D043587:Receptor, Muscarinic M3