Evaluation of muscarinic acetylcholine receptor type 3 gene polymorphisms in patients with primary biliary cholangitis and primary sclerosing cholangitis

Lena Maria Greverath, Elise Leicht, Nina Wald de Chamorro, Anne Christin Beatrice Wilde, Lara Marleen Steinhagen, Charlotte Lieb, Moritz Schmelzle, Sascha Chopra, Oren Shibolet, Janett Fischer, Thomas Berg, Frank Tacke, Tobias Müller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Aim: Muscarinic acetylcholine receptor type 3-mediated signaling might be involved in the pathogenesis of chronic inflammatory biliary diseases, such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). The aim of the present study was to investigate the prevalence of five well-characterized specific single-nucleotide polymorphisms within the muscarinic acetylcholine receptor type 3 gene, CHRM3 (rs11578320, rs6690809, rs6429157, rs7548522, and rs4620530), in patients with PBC and PSC. Patients with chronic hepatitis C (CHC) and healthy individuals served as control cohorts. In the PBC cohort, baseline characteristics and response to ursodeoxycholic acid therapy applying established response criteria at 12 months after the initiation of treatment were evaluated according to the underlying CHRM3 genotype. Methods: CHRM3 genotyping was carried out in 306 PBC patients, 205 PSC patients, 208 CHC patients, and 240 healthy controls from two independent German tertiary care university centers in Berlin and Leipzig, Germany. Results: CHRM3 rs4620530 proportions in patients with PBC significantly differed from patients with PSC (P = 0.005), CHC (P = 0.009), and healthy controls (P = 0.008), primarily due to a substantial overrepresentation of the T allele in PBC (49.3% in PBC vs. 39.8% in PSC, 35.7% in CHC, and 40% in healthy controls), indicating a potential association of the rs4620530 T allele with PBC (OR 1.461, 95% CI 1.147–1.861, P = 0.002). Further analysis showed no association of CHRM3 single-nucleotide polymorphism rs4620530 with baseline characteristics and ursodeoxycholic acid treatment response in PBC. Conclusion: CHRM3 single-nucleotide polymorphism rs4620530 might confer an increased genetic risk for the development of PBC.

Original languageEnglish
Pages (from-to)321-329
Number of pages9
JournalHepatology Research
Issue number3
StatePublished - 1 Mar 2020


FundersFunder number
Barbara Malik
German Research CommunityMU 2864/1-3


    • biliary bicarbonate umbrella
    • chronic biliary inflammation
    • muscarinic acetylcholine receptor type 3
    • primary biliary cholangitis
    • primary sclerosing cholangitis
    • ursodeoxycholic acid


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