Potential association of muscarinic receptor 3 gene variants with primary Sjögren's syndrome

Appel, Silke; Le Hellard, Stephanie; Bruland, Ove; Brun, Johan G; Omdal, Roald; Kristjansdottir, Gudlaug; Theander, Elke; Nordmark, Gunnel; Kvarnström, Marika; Eriksson, Per; Rönnblom, Lars; Wahren-Herlenius, Marie; Jonsson, Roland

doi:10.1136/ard.2010.138966

Potential association of muscarinic receptor 3 gene variants with primary Sjögren's syndrome

¹Broegelmann Research Laboratory, The Gade Institute, University of Bergen, Bergen, Norway
²Department of Clinical Medicine, University of Bergen, Bergen, Norway
³Center for Medical Genetics and Molecular Medicine, Haukeland University Hospital, Bergen, Norway
⁴Department of Rheumatology, Haukeland University Hospital, Bergen, Norway
⁵Section for Rheumatology, Institute of Medicine, University of Bergen, Bergen, Norway
⁶Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway
⁷Institute of Internal Medicine, University of Bergen, Bergen, Norway
⁸Molecular Medicine, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
⁹Section of Rheumatology, Department of Medical Sciences, Uppsala University, Uppsala, Sweden
¹⁰Department of Rheumatology, Malmö University Hospital, Malmö, Sweden
¹¹Rheumatology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden
¹²Department of Rheumatology, University Hospital, Linköping, Sweden

Correspondence to Dr Silke Appel, Broegelmann Research Laboratory, The Gade Institute, Laboratory Building 5th Floor, 5021 Bergen, Norway; silke.appel{at}gades.uib.no

Accepted 2 March 2011
Published Online First 30 March 2011

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.

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.