Greverath Lena Maria, Leicht Elise, Wald de Chamorro Nina, Wilde Anne-Christin Beatrice, Steinhagen Lara Marleen, Lieb Charlotte, Schmelzle Moritz, Chopra Sascha, Shibolet Oren, Fischer Janett, Berg Thomas, Tacke Frank, Müller Tobias
Medizinische Klinik mit Schwerpunkt Hepatologie und Gastroenterologie, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
Chirurgische Klinik, Charité - Universitätsmedizin Berlin, Campus Virchow Klinikum, Berlin, Germany.
Hepatol Res. 2020 Mar;50(3):321-329. doi: 10.1111/hepr.13455. Epub 2019 Dec 3.
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.
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.
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.
CHRM3 single-nucleotide polymorphism rs4620530 might confer an increased genetic risk for the development of PBC.
毒蕈碱型乙酰胆碱受体3介导的信号传导可能参与慢性炎症性胆道疾病的发病机制，如原发性胆汁性胆管炎（PBC）和原发性硬化性胆管炎（PSC）。本研究的目的是调查PBC和PSC患者中，毒蕈碱型乙酰胆碱受体3基因（CHRM3）内五个特征明确的特定单核苷酸多态性（rs11578320、rs6690809、rs6429157、rs7548522和rs4620530）的流行情况。丙型慢性肝炎（CHC）患者和健康个体作为对照队列。在PBC队列中，根据潜在的CHRM3基因型，评估基线特征以及按照既定的治疗后12个月反应标准对熊去氧胆酸治疗的反应。
对来自德国柏林和莱比锡两个独立的德国三级医疗大学中心的306例PBC患者、205例PSC患者、208例CHC患者和240例健康对照进行CHRM3基因分型。
PBC患者中CHRM3 rs4620530的比例与PSC患者（P = 0.005）、CHC患者（P = 0.009）和健康对照（P = 0.008）有显著差异，主要是由于PBC中T等位基因的比例显著过高（PBC中为49.3%，PSC中为39.8%，CHC中为35.7%，健康对照中为40%），表明rs4620530 T等位基因与PBC可能存在关联（OR 1.461，95% CI 1.147 - 1.861，P = 0.002）。进一步分析显示，CHRM3单核苷酸多态性rs4620530与PBC的基线特征和熊去氧胆酸治疗反应无关。
CHRM3单核苷酸多态性rs4620530可能会增加PBC发生的遗传风险。
