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.
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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Authors: Orsia D Konsta; Christelle Le Dantec; Amandine Charras; Wesley H Brooks; Marina I Arleevskaya; Anne Bordron; Yves Renaudineau Journal: Front Immunol Date: 2015-08-26 Impact factor: 7.561
Authors: Sarah Pringle; Xiaoyan Wang; Gwenny M P J Verstappen; Janneke H Terpstra; Clarence K Zhang; Aiqing He; Vishal Patel; Rhiannon E Jones; Duncan M Baird; Fred K L Spijkervet; Arjan Vissink; Hendrika Bootsma; Robert P Coppes; Frans G M Kroese Journal: Arthritis Rheumatol Date: 2019-01 Impact factor: 10.995
Authors: José Santiago Ibáñez-Cabellos; Marta Seco-Cervera; Rebeca Osca-Verdegal; Federico V Pallardó; José Luis García-Giménez Journal: Front Genet Date: 2019-11-13 Impact factor: 4.599