5 results on '"Greverath, Lena Maria"'
Search Results
2. Untersuchung zur Bedeutung genetischer Polymorphismen des muskarinergen Acetylcholinrezeptors Typ 3 bei chronisch-entzündlichen Gallengangserkrankungen
- Author
-
Greverath, Lena Maria
- Subjects
Primary Biliary Cholangitis ,Primary Sclerosing Cholangitis ,Muscarinic Acetylcholine Receptor Type 3 ,digestive system ,digestive system diseases ,600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit - Abstract
Einleitung: Dysfunktionale Signalwege des muskarinergen Acetylcholinrezeptor Typ 3 (mAChR3) könnten durch eine Beeinträchtigung der biliären Bikarbonatsekretion an der Pathogenese von chronisch-entzündlichen Gallengangserkrankungen wie der primär biliären Cholangitis (PBC) und der primär sklerosierenden Cholangitis (PSC) beteiligt sein. Ziel der vorliegenden Studie war, die mögliche Bedeutung der bekannten Einzelpunktmutationen (Single Nucleotide Polymorphism, SNP) rs11578320, rs6690809, rs6429157, rs7548522 und rs4620530 im Gen des mAChR3 (CHRM3) bei Patient*innen mit PBC, PSC, chronischer Hepatitis C (CHC), sowie einer Kontrollkohorte mit gesunden Proband*innen zu untersuchen. Methoden: Bei 306 Patient*innen mit PBC, 205 Patient*innen mit PSC, 208 Patient*innen mit CHC und 240 gesunden Proband*innen der Universitätskliniken Berlin und Leipzig wurden mittels Polymerasekettenreaktion und Schmelzkurvenanalyse die Genotypen der CHRM3-SNPs bestimmt. In der PBC-Kohorte wurden zusätzlich Daten bezüglich der allgemeinen klinischen und paraklinischen Charakteristika erhoben, sowie das Therapieansprechen auf Ursodesoxycholsäure (UDCA) nach 12 Monaten in Relation zu dem zugrundeliegenden CHRM3-Genotyp untersucht. Desweiteren wurden mAChR3-Expressionsanalysen in explantiertem Lebergewebe von Patient*innen mit PBC und PSC durchgeführt, um die Expression des mAChR3 in Abhängigkeit des CHRM3-Genotyps zu untersuchen. Ergebnisse: Die Untersuchungen zu SNP rs4620530 des CHRM3-Gens zeigten sowohl signifikante Unterschiede hinsichtlich der Verteilung der Genotypen zwischen PBC-Patient*innen und der gesunden Kontrollgruppe (p=0,008), als auch zwischen PBC- und den PSC- und CHC-Patient*innen (p=0,005 beziehungsweise p=0,009). Dies ließ sich auf Unterschiede im Vorkommen des T-Allels zurückführen, welches in PBC-Patient*innen zu 49,3%, bei PSC-Patient*innen zu 39,8%, bei CHC-Patient*innen zu 35,7% und in den gesunden Kontrollen zu 40% nachgewiesen werden konnte. Das CHRM3 rs4620530 T-Allel war dabei mit dem Vorkommen einer PBC assoziiert (odds ratio [OR] =1,461, 95% confidence interval [CI] 1,147-1,861, p=0,002). Bei den PBC Patient*innen zeigten jedoch initiale Laborparameter, Komorbiditäten und Einjahres-Therapieansprechen auf UDCA anhand von etablierten Kriterien keine signifikanten Unterschiede zwischen den verschiedenen Genotypen des CHRM3 rs4620540. In Immunblots an Gewebe explantierter Lebern von PBC- und PSC-Erkrankten konnte die Expression des mAChR3 speziell in den Gallengängen nachgewiesen werden. Das Expressionsmuster zeigte jedoch keine spezifischen Veränderungen im Vergleich der verschiedenen Genotypen des CHRM3 rs4620540. Schlussfolgerung: Das T-Allel des SNP rs4620530 im CHRM3-Gen scheint ein potentieller genetischer Risikofaktor für die PBC zu sein., Introduction: An impaired function of the muscarinic acetylcholine receptor type 3 (mAChR3) might be involved in an altered bicarbonate secretion in bile ducts. This presumably leads to 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 (SNP) within the CHRM3 gene (rs11578320, rs6690809, rs6429157, rs7548522 and rs4620530) in patients with PBC and PSC. Patients with chronic hepatitis C (CHC) and healthy individuals (HC) served as respective control cohorts. Methods: Using PCR and melt curve analysis, CHRM3 genotyping was performed in 306 PBC patients, 205 PSC patients, 208 patients with CHC and 240 HC from two independent tertiary care university centers in Berlin and Leipzig in Germany. In PBC patients baseline characteristics and response to ursodeoxycholic acid (UDCA) therapy applying established response criteria at 12 months after the initiation of UDCA treatment were also evaluated according to the underlying CHRM3 genotype. To evaluate the expression of mAChR3 in relation to the underlying CHRM3 genotype, immunofluorescence and immunoblots have been performed on explanted liver tissue from PBC and PSC patients. Results: The CHRM3 rs4620530 genotype distribution in patients with PBC significantly differed from patients with PSC (p=0.005), CHC (p=0.009) and healthy controls (p=0.008), which was primarily due to a substantial over-representation of the T allele in PBC (49.3% in PBC versus 39.8% in PSC, 35.7% in CHC and 40% in HC). This indicated a potential association of the rs4620530 T allele with PBC (odds ratio [OR] = 1.461, 95% confidence interval [CI] 1.147-1.861; p=0.002). The prevalence of TT/TG genotypes was significantly higher in patients with PBC compared to patients with PSC (74.5% vs. 61.0%; p=0.001) and patients with CHC (74.5% vs. 63.5%). Further analysis revealed no obvious correlation with baseline characteristics and UDCA treatment response in patients with PBC. Immunblots of explanted liver tissue from PBC patients exhibited specific expression of mAChR3 exclusively in bile ducts, but no obvious variance in the expression pattern in-between genotypes of rs4620530. Conclusion: The T allele of CHRM3 SNP rs4620530 was identified as a potential genetic risk factor for the development of PBC.
- Published
- 2021
- Full Text
- View/download PDF
3. Real-World Clinical Management of Patients with Primary Biliary Cholangitis—A Retrospective Multicenter Study from Germany
- Author
-
Wilde, Anne-Christin Beatrice, primary, Lieb, Charlotte, additional, Leicht, Elise, additional, Greverath, Lena Maria, additional, Steinhagen, Lara Marleen, additional, Wald de Chamorro, Nina, additional, Petersen, Jörg, additional, Hofmann, Wolf Peter, additional, Hinrichsen, Holger, additional, Heyne, Renate, additional, Berg, Thomas, additional, Naumann, Uwe, additional, Schwenzer, Jeannette, additional, Vermehren, Johannes, additional, Geier, Andreas, additional, Tacke, Frank, additional, and Müller, Tobias, additional
- Published
- 2021
- Full Text
- View/download PDF
4. Evaluation of muscarinic acetylcholine receptor type 3 gene polymorphisms in patients with primary biliary cholangitis and primary sclerosing cholangitis
- Author
-
Greverath, Lena Maria, primary, Leicht, Elise, additional, Wald de Chamorro, Nina, additional, Wilde, Anne‐Christin Beatrice, additional, Steinhagen, Lara Marleen, additional, Lieb, Charlotte, additional, Schmelzle, Moritz, additional, Chopra, Sascha, additional, Shibolet, Oren, additional, Fischer, Janett, additional, Berg, Thomas, additional, Tacke, Frank, additional, and Müller, Tobias, additional
- Published
- 2019
- Full Text
- View/download PDF
5. Evaluation of muscarinic acetylcholine receptor type 3 gene polymorphisms in patients with primary biliary cholangitis and primary sclerosing cholangitis.
- Author
-
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, and Müller, Tobias
- Subjects
- *
MUSCARINIC acetylcholine receptors , *CHOLANGITIS , *SINGLE nucleotide polymorphisms , *GENETIC polymorphisms , *CHRONIC hepatitis C , *URSODEOXYCHOLIC acid - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.