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Potential association of muscarinic receptor 3 gene variants with primary Sjögren's syndrome
  1. Silke Appel1,
  2. Stephanie Le Hellard2,3,
  3. Ove Bruland3,
  4. Johan G Brun4,5,
  5. Roald Omdal6,7,
  6. Gudlaug Kristjansdottir8,9,
  7. Elke Theander10,
  8. Gunnel Nordmark9,
  9. Marika Kvarnström11,
  10. Per Eriksson12,
  11. Lars Rönnblom9,
  12. Marie Wahren-Herlenius11,
  13. Roland Jonsson1,4
  1. 1Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway
  2. 2Department of Clinical Medicine, University of Bergen, Bergen, Norway
  3. 3Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
  4. 4Department of Rheumatology, Haukeland University Hospital, Bergen, Norway
  5. 5Section for Rheumatology, Institute of Medicine, University of Bergen, Bergen, Norway
  6. 6Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway
  7. 7Institute of Internal Medicine, University of Bergen, Bergen, Norway
  8. 8Molecular Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  9. 9Section of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
  10. 10Department of Rheumatology, Malmö University Hospital, Malmö, Sweden
  11. 11Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
  12. 12Department of Rheumatology, University Hospital, Linköping, Sweden
  1. Correspondence to Dr Silke Appel, Broegelmann Research Laboratory, The Gade Institute, Laboratory Building 5th Floor, 5021 Bergen, Norway; silke.appel{at}gades.uib.no

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.

Conclusion 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.

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Footnotes

  • Funding Financial support was obtained from Bergens Forskningsstiftelsen, Kreftforeningen, the Broegelmann Foundation, the Western Norway Regional Health Authority, the Strategic Research Program at Helse Bergen, the Swedish Research Council, the Swedish Rheumatism Association, the Gustafsson Foundation, the King Gustaf V 80th Birthday Foundation, Söderberg's Foundation and COMBINE.

  • Competing interests None.

  • Ethics approval The study was approved by the relevant ethical committees.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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