Analysis of GPRC6A variants in different pancreatitis etiologies

Autor: Markus M. Lerch, Emmanuelle Masson, Joost P.H. Drenth, Peter Bugert, Jian-Min Chen, Wen Bin Zou, Marko Damm, Matthias Sendler, Jonas Rosendahl, Heidi Griesmann, Holger Kirsten, Claudia Ruffert, Ewa Małecka-Panas, Markus Scholz, Nico Hesselbarth, Tom Kaune, Rene H. M. te Morsche, Péter Hegyi, Stanisław Głuszek, Zhuan Liao, Julian Cardinal von Widdern, Heiko Witt, Raffaella Alessia Zuppardo, Robert Grützmann, Louis Buscail, Sebastian Krug, Shun Jiang Deng, Frank Ulrich Weiss, Vinciane Rebours, Giulia Martina Cavestro, Claude Férec, Adrian Saftoiu, Patrick Michl
Přispěvatelé: Kaune, T., Ruffert, C., Hesselbarth, N., Damm, M., Krug, S., Cardinal von Widdern, J., Masson, E., Chen, J. -M., Rebours, V., Buscail, L., Ferec, C., Grutzmann, R., te Morsche, R. H. M., Drenth, J. P., Cavestro, G. M., Zuppardo, R. A., Saftoiu, A., Malecka-Panas, E., Gluszek, S., Bugert, P., Lerch, M. M., Sendler, M., Weiss, F. U., Zou, W. -B., Deng, S. -J., Liao, Z., Scholz, M., Kirsten, H., Hegyi, P., Witt, H., Michl, P., Griesmann, H., Rosendahl, J.
Rok vydání: 2020
Předmět:
Adult
Male
Candidate gene
Pancreatitis
Alcoholic
Endocrinology
Diabetes and Metabolism
Single-nucleotide polymorphism
Polymorphism
Single Nucleotide
White People
Receptors
G-Protein-Coupled
03 medical and health sciences
0302 clinical medicine
Asian People
Risk Factors
Genetics
Humans
Medicine
SNP
Genetic Predisposition to Disease
Aged
Inflammation
Hepatology
G-Protein coupled receptor
business.industry
Gastroenterology
Genetic Variation
Inflammasome
DNA
Odds ratio
Middle Aged
Tag SNP
medicine.disease
Europe
Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11]
Pancreatitis
030220 oncology & carcinogenesis
Cohort
Immunology
Female
Calcium
030211 gastroenterology & hepatology
business
Receptors
Calcium-Sensing
Genome-Wide Association Study
Signal Transduction
medicine.drug
Zdroj: Pancreatology, 20, 1262-1267
Pancreatology, 20, 7, pp. 1262-1267
ISSN: 1424-3903
Popis: Contains fulltext : 229360.pdf (Publisher’s version ) (Closed access) BACKGROUND: The G-protein-coupled receptor Class C Group 6 Member A (GPRC6A) is activated by multiple ligands and is important for the regulation of calcium homeostasis. Extracellular calcium is capable to increase NLRP3 inflammasome activity of the innate immune system and deletion of this proinflammatory pathway mitigated pancreatitis severity in vivo. As such this pathway and the GPRC6A receptor is a reasonable candidate gene for pancreatitis. Here we investigated the prevalence of sequence variants in the GPRC6A locus in different pancreatitis aetiologies. METHODS: We selected 6 tagging SNPs with the SNPinfo LD TAG SNP Selection tool and the functional relevant SNP rs6907580 for genotyping. Cohorts from Germany, further European countries and China with up to 1,124 patients and 1,999 controls were screened for single SNPs with melting curve analysis. RESULTS: We identified an association of rs1606365(G) with alcoholic chronic pancreatitis in a German (odds ratio (OR) 0.76, 95% confidence interval (CI) 0.65-0.89, p = 8 × 10(-5)) and a Chinese cohort (OR 0.78, 95% CI 0.64-0.96, p = 0.02). However, this association was not replicated in a combined cohort of European patients (OR 1.18, 95% CI 0.99-1.41, p = 0.07). Finally, no association was found with acute and non-alcoholic chronic pancreatitis. CONCLUSIONS: Our results support a potential role of calcium sensing receptors and inflammasome activation in alcoholic chronic pancreatitis development. As the functional consequence of the associated variant is unclear, further investigations might elucidate the relevant mechanisms.
Databáze: OpenAIRE
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