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. 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.

journal_name

Ann Rheum Dis

authors

Appel S,Le Hellard S,Bruland O,Brun JG,Omdal R,Kristjansdottir G,Theander E,Nordmark G,Kvarnström M,Eriksson P,Rönnblom L,Wahren-Herlenius M,Jonsson R

doi

10.1136/ard.2010.138966

subject

Has Abstract

pub_date

2011-07-01 00:00:00

pages

1327-9

issue

7

eissn

0003-4967

issn

1468-2060

pii

ard.2010.138966

journal_volume

70

pub_type

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