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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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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