TRPV6 variants confer susceptibility to chronic pancreatitis in the Chinese population.
TRPV6 gene
calcium signaling
chronic pancreatitis
low-coverage whole-genome sequencing
missense variants
Journal
Human mutation
ISSN: 1098-1004
Titre abrégé: Hum Mutat
Pays: United States
ID NLM: 9215429
Informations de publication
Date de publication:
08 2020
08 2020
Historique:
received:
02
01
2020
revised:
28
04
2020
accepted:
04
05
2020
pubmed:
10
5
2020
medline:
9
11
2021
entrez:
9
5
2020
Statut:
ppublish
Résumé
Chronic pancreatitis (CP) is a progressive fibroinflammatory syndrome of the pancreatic tissue caused by genetic and environmental factors. Previously reported susceptibility genes in CP explain less than half of the apparent heritability. To uncover novel pathogenic mechanisms, we initially performed low-coverage whole-genome sequencing on 464 Chinese CP patients and 504 controls. The transient receptor potential cation channel, Subfamily V, Member 6 (TRPV6) gene was found to be significantly associated with CP after a burden test of aggregated rare nonsynonymous variants with a combined annotation dependent depletion score > 20 (p = .020). In the replication stage, we analyzed the entire coding sequence and exon/intron boundaries of the TPRV6 gene by Sanger sequencing in another 205 patients with CP and 105 controls. Integration of the findings from the two stages resulted in the identification of 25 TRPV6 variants: 1 rare nonsense variant, 20 rare missense variants, and 4 common missense variants. Loss-of-function variants, as determined by intracellular Ca
Substances chimiques
Calcium Channels
0
Codon, Nonsense
0
TRPV Cation Channels
0
TRPV6 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1351-1357Informations de copyright
© 2020 Wiley Periodicals LLC.
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