The three common polymorphisms p.A986S, p.R990G and p.Q1011E in the calcium sensing receptor (CASR) are not associated with chronic pancreatitis.

Autor: Ewers M; Pediatric Nutritional Medicine & Else Kröner-Fresenius-Centre for Nutritional Medicine (EKFZ), Technical University Munich (TUM), Freising, Germany., Canaff L; Departments of Medicine and Physiology, McGill University Health Centre, McGill University, Montréal, Québec, Canada., Weh AE; Pediatric Nutritional Medicine & Else Kröner-Fresenius-Centre for Nutritional Medicine (EKFZ), Technical University Munich (TUM), Freising, Germany., Masson E; Univ Brest, Inserm, EFS, UMR 1078, GGB, F-29200, Brest, France; Service de Génétique Médicale et de Biologie de La Reproduction, CHRU Brest, F-29200, Brest, France., Eiseler K; Pediatric Nutritional Medicine & Else Kröner-Fresenius-Centre for Nutritional Medicine (EKFZ), Technical University Munich (TUM), Freising, Germany., Chen JM; Univ Brest, Inserm, EFS, UMR 1078, GGB, F-29200, Brest, France., Rebours V; Department of Gastroenterology and Pancreatology, Beaujon Hospital, Assistance Publique-Hôpitaux de Paris, Clichy, Université de Paris, Paris, France., Bugert P; Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service of Baden-Württemberg, Mannheim, Germany., Michl P; Department of Internal Medicine I, Martin Luther University, Halle, Germany., Rosendahl J; Department of Internal Medicine I, Martin Luther University, Halle, Germany., Férec C; Univ Brest, Inserm, EFS, UMR 1078, GGB, F-29200, Brest, France; Service de Génétique Médicale et de Biologie de La Reproduction, CHRU Brest, F-29200, Brest, France., Goltzman D; Departments of Medicine and Physiology, McGill University Health Centre, McGill University, Montréal, Québec, Canada., Witt H; Pediatric Nutritional Medicine & Else Kröner-Fresenius-Centre for Nutritional Medicine (EKFZ), Technical University Munich (TUM), Freising, Germany. Electronic address: heiko.witt@tum.de.
Jazyk: angličtina
Zdroj: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] [Pancreatology] 2021 Oct; Vol. 21 (7), pp. 1299-1304. Date of Electronic Publication: 2021 Aug 21.
DOI: 10.1016/j.pan.2021.08.008
Abstrakt: Background: The calcium sensing receptor (CASR) is a G protein-coupled receptor that is responsible for assessing extracellular Ca 2+ levels and thus plays a crucial role in calcium homeostasis. Hypercalcemia is a metabolic risk factor for pancreatitis and rare CASR variants have been described in patients with chronic pancreatitis. At the carboxy-terminal tail of CASR, there is a cluster of three common polymorphisms, p.A986S (rs1801725), p.R990G (rs1042636) and p.Q1011E (rs1801726), which have been associated with chronic pancreatitis in various studies, but with conflicting results.
Methods: We examined 542 German and 339 French patients with chronic pancreatitis as well as 1025 German controls for the 3 common CASR polymorphism by melting curve analysis. For comparison, we used genotype data from 583 French controls from a previous study. In addition, we functionally analyzed the three variants by NFAT and SRE luciferase reporter systems as well as Western blotting and verified cell surface expression by ELISA.
Results: In both cohorts, neither the genotype nor the allele frequencies differed significantly between patients and controls. In both luciferase assays, p.R990G showed a significant leftward shift, indicating an increased responsiveness of the receptor. p.A986S showed a leftward shift in the SRE but not in the NFAT reporter assay, while the responsiveness of p.Q1011E did not differ from the wild-type. These functional studies therefore do not support the contributions of variant CASR to increasing the risk of pancreatitis.
Conclusions: The three frequent CASR polymorphisms are unlikely to increase the risk for chronic pancreatitis.
Competing Interests: Declaration of competing interest The authors report no conflicts of interest.
(Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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