Glycoprotein 2 in health and disease: lifting the veil
Open Access
- 3 December 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in Genes and Environment
- Vol. 43 (1), 1-9
- https://doi.org/10.1186/s41021-021-00229-8
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).Keywords
Funding Information
- Ministry of Education, Culture, Sports, Science and Technology (21H03186)
This publication has 37 references indexed in Scilit:
- Meta-analysis identifies common variants associated with body mass index in east AsiansNature Genetics, 2012
- Abundant Pleiotropy in Human Complex Diseases and TraitsAmerican Journal of Human Genetics, 2011
- Genetic Analysis of the Glycoprotein 2 Gene in Patients With Chronic PancreatitisPancreas, 2010
- The c.1275A>G putative chronic pancreatitis-associated synonymous polymorphism in the glycoprotein 2 (GP2) gene decreases exon 9 inclusionMolecular Genetics and Metabolism, 2010
- Mutational Analysis of the Gene Encoding the Zymogen Granule Membrane Glycoprotein 2 (GP2) in Patients With Chronic PancreatitisPancreas, 2010
- The pancreatic zymogen granule membrane protein, GP2, binds Escherichia colitype 1 FimbriaeBMC Gastroenterology, 2009
- Predicting the effects of coding non-synonymous variants on protein function using the SIFT algorithmNature Protocols, 2009
- Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetesNature Genetics, 2009
- ZONA PELLUCIDA DOMAIN PROTEINSAnnual Review of Biochemistry, 2005
- Complement Factor H Polymorphism in Age-Related Macular DegenerationScience, 2005