Glycoprotein 2 in health and disease: lifting the veil

Abstract In 2020, we discovered glycoprotein 2 (GP2) variants associated with pancreatic cancer susceptibility in a genome-wide association study involving the Japanese population. Individuals carrying a missense coding variant (rs78193826) in the GP2 gene resulting in a p.V432M substitution had an...

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Autores principales:	Yingsong Lin, Masahiro Nakatochi, Naoki Sasahira, Makoto Ueno, Naoto Egawa, Yasushi Adachi, Shogo Kikuchi
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	GP2 Pancreas Acinar cells UMOD Antibacterial Genome-wide association study Ecology QH540-549.5 Genetics QH426-470
Acceso en línea:	https://doaj.org/article/cd86520684ce48759ed48882ac9f59ca
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spelling	oai:doaj.org-article:cd86520684ce48759ed48882ac9f59ca2021-12-05T12:10:41ZGlycoprotein 2 in health and disease: lifting the veil10.1186/s41021-021-00229-81880-7062https://doaj.org/article/cd86520684ce48759ed48882ac9f59ca2021-12-01T00:00:00Zhttps://doi.org/10.1186/s41021-021-00229-8https://doaj.org/toc/1880-7062Abstract In 2020, we discovered glycoprotein 2 (GP2) variants associated with pancreatic cancer susceptibility in a genome-wide association study involving the Japanese population. Individuals carrying a missense coding variant (rs78193826) in the GP2 gene resulting in a p.V432M substitution had an approximately 1.5-fold higher risk of developing pancreatic cancer than those without this variant. GP2 is expressed on the inner surface of zymogen granules in pancreatic acinar cells, which are responsible for the sorting, storage and secretion of digestive enzymes. Upon neuronal, hormonal, or other stimulation, GP2 is cleaved from the membrane of zymogen granules and then secreted into the pancreatic duct and intestinal lumen. While the functions of GP2 remain poorly understood, emerging evidence suggests that it plays an antibacterial role in the gastrointestinal tract after being secreted from pancreatic acinar cells. Impaired GP2 functions may facilitate the adhesion of bacteria to the intestinal mucosa. In this review article, we summarize the role of GP2 in health and disease, emphasizing its functions in the gastrointestinal tract, as well as genetic variations in the GP2 gene and their associations with disease susceptibility. We hope that its robust genetic associations with pancreatic cancer, coupled with its emerging role in gastrointestinal mucosal immunity, will spur renewed research interest in GP2, which has been understudied over the past 30 years compared with its paralog uromodulin (UMOD).Yingsong LinMasahiro NakatochiNaoki SasahiraMakoto UenoNaoto EgawaYasushi AdachiShogo KikuchiBMCarticleGP2PancreasAcinar cellsUMODAntibacterialGenome-wide association studyEcologyQH540-549.5GeneticsQH426-470ENGenes and Environment, Vol 43, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	GP2 Pancreas Acinar cells UMOD Antibacterial Genome-wide association study Ecology QH540-549.5 Genetics QH426-470
spellingShingle	GP2 Pancreas Acinar cells UMOD Antibacterial Genome-wide association study Ecology QH540-549.5 Genetics QH426-470 Yingsong Lin Masahiro Nakatochi Naoki Sasahira Makoto Ueno Naoto Egawa Yasushi Adachi Shogo Kikuchi Glycoprotein 2 in health and disease: lifting the veil
description	Abstract In 2020, we discovered glycoprotein 2 (GP2) variants associated with pancreatic cancer susceptibility in a genome-wide association study involving the Japanese population. Individuals carrying a missense coding variant (rs78193826) in the GP2 gene resulting in a p.V432M substitution had an approximately 1.5-fold higher risk of developing pancreatic cancer than those without this variant. GP2 is expressed on the inner surface of zymogen granules in pancreatic acinar cells, which are responsible for the sorting, storage and secretion of digestive enzymes. Upon neuronal, hormonal, or other stimulation, GP2 is cleaved from the membrane of zymogen granules and then secreted into the pancreatic duct and intestinal lumen. While the functions of GP2 remain poorly understood, emerging evidence suggests that it plays an antibacterial role in the gastrointestinal tract after being secreted from pancreatic acinar cells. Impaired GP2 functions may facilitate the adhesion of bacteria to the intestinal mucosa. In this review article, we summarize the role of GP2 in health and disease, emphasizing its functions in the gastrointestinal tract, as well as genetic variations in the GP2 gene and their associations with disease susceptibility. We hope that its robust genetic associations with pancreatic cancer, coupled with its emerging role in gastrointestinal mucosal immunity, will spur renewed research interest in GP2, which has been understudied over the past 30 years compared with its paralog uromodulin (UMOD).
format	article
author	Yingsong Lin Masahiro Nakatochi Naoki Sasahira Makoto Ueno Naoto Egawa Yasushi Adachi Shogo Kikuchi
author_facet	Yingsong Lin Masahiro Nakatochi Naoki Sasahira Makoto Ueno Naoto Egawa Yasushi Adachi Shogo Kikuchi
author_sort	Yingsong Lin
title	Glycoprotein 2 in health and disease: lifting the veil
title_short	Glycoprotein 2 in health and disease: lifting the veil
title_full	Glycoprotein 2 in health and disease: lifting the veil
title_fullStr	Glycoprotein 2 in health and disease: lifting the veil
title_full_unstemmed	Glycoprotein 2 in health and disease: lifting the veil
title_sort	glycoprotein 2 in health and disease: lifting the veil
publisher	BMC
publishDate	2021
url	https://doaj.org/article/cd86520684ce48759ed48882ac9f59ca
work_keys_str_mv	AT yingsonglin glycoprotein2inhealthanddiseaseliftingtheveil AT masahironakatochi glycoprotein2inhealthanddiseaseliftingtheveil AT naokisasahira glycoprotein2inhealthanddiseaseliftingtheveil AT makotoueno glycoprotein2inhealthanddiseaseliftingtheveil AT naotoegawa glycoprotein2inhealthanddiseaseliftingtheveil AT yasushiadachi glycoprotein2inhealthanddiseaseliftingtheveil AT shogokikuchi glycoprotein2inhealthanddiseaseliftingtheveil
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Glycoprotein 2 in health and disease: lifting the veil

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