Analysis of GPRC6A variants in different pancreatitis etiologies.

Adult Aged Asian People DNA / genetics Europe Female Genetic Predisposition to Disease Genetic Variation Genome-Wide Association Study Humans Male Middle Aged Pancreatitis / genetics Pancreatitis, Alcoholic / genetics Polymorphism, Single Nucleotide Receptors, Calcium-Sensing / genetics Receptors, G-Protein-Coupled / genetics Risk Factors Signal Transduction / genetics White People

Calcium G-Protein coupled receptor Genetics Inflammation Pancreatitis

Journal

Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.]

ISSN: 1424-3911

Titre abrégé: Pancreatology

Pays: Switzerland

ID NLM: 100966936

Informations de publication

Date de publication:
Oct 2020

Historique:

received: 22 05 2020

revised: 09 07 2020

accepted: 02 08 2020

pubmed: 30 8 2020

medline: 18 9 2021

entrez: 30 8 2020

Statut: ppublish

Résumé

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. 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. 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 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.

Sections du résumé

BACKGROUND BACKGROUND

METHODS 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 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

CONCLUSIONS 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.

Identifiants

DOI: 10.1016/j.pan.2020.08.001 PMID: 32859544

pubmed: 32859544

pii: S1424-3903(20)30650-5

doi: 10.1016/j.pan.2020.08.001

pii:

doi:

Substances chimiques

GPRC6A protein, human 0

Receptors, Calcium-Sensing 0

Receptors, G-Protein-Coupled 0

DNA 9007-49-2

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

1262-1267

Informations de copyright

Déclaration de conflit d'intérêts

Declaration of competing interest The authors report no conflicts of interest.