Variants in pancreatic carboxypeptidase genes CPA2 and CPB1 are not associated with chronic pancreatitis

American Journal of Physiology. Gastrointestinal and Liver Physiology
Eriko NakanoHeiko Witt

Abstract

Genetic alterations in the carboxypeptidase A1 gene (CPA1) are associated with early onset chronic pancreatitis (CP). Besides CPA1, there are two other human pancreatic carboxypeptidases (CPA2 and CPB1). Here we examined whether CPA2 and CPB1 alterations are associated with CP in Japan and Germany. All exons and flanking introns of CPA2 and CPB1 were sequenced in 477 Japanese patients with CP (234 alcoholic, 243 nonalcoholic) and in 497 German patients with nonalcoholic CP by targeted next-generation sequencing and/or Sanger sequencing. Secretion and enzymatic activity of CPA2 and CPB1 variants were determined after transfection into HEK 293T cells. We identified six nonsynonymous CPA2 variants (p.V67I, p.G166R, p.D168E, p.D173H, p.R237W, and p.G388S), eight nonsynonymous CPB1 alterations (p.S65G, p.N120S, p.D172E, p.R195H, p.D208N, p.F232L, p.A317V, and p.D364Y), and one splice-site variant (c.687+1G>T) in CPB1. Functional analysis revealed essentially complete loss of function in CPA2 variants p.R237W and p.G388S and CPB1 variants p.R110H and p.D364Y. None of the CPA2 or CPB1 variants, including those resulting in a marked loss of function, were overrepresented in patients with CP. In conclusion, CPA2 and CPB1 variants are no...Continue Reading

References

Apr 1, 1992·Protein Science : a Publication of the Protein Society·M A PhillipsW J Rutter
Jun 1, 1995·The New England Journal of Medicine·M L SteerS Freedman
Feb 17, 2001·Gastroenterology·B Etemad, D C Whitcomb
Mar 16, 2004·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Nathan HowesUNKNOWN European Registry of Hereditary Pancreatitis and Pancreatic Cancer (EUROPAC)
Nov 26, 2010·The Journal of Biological Chemistry·Richárd SzmolaMiklós Sahin-Tóth
Apr 28, 2012·The Journal of Biological Chemistry·András Szabó, Miklós Sahin-Tóth
Aug 21, 2013·Nature Genetics·Heiko WittMiklós Sahin-Tóth
Feb 14, 2014·The Tohoku Journal of Experimental Medicine·Atsushi Masamune

❮ Previous
Next ❯

Citations

Jul 12, 2016·Pancreatology : Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]·Atsushi MasamuneTooru Shimosegawa
Jul 14, 2016·Journal of Pediatric Gastroenterology and Nutrition·Nobutomo SaitoToshiaki Shimizu
Apr 20, 2018·Proceedings of the National Academy of Sciences of the United States of America·Koji TamuraMichael Goggins
Jul 1, 2016·The Journal of Biological Chemistry·András SzabóMiklós Sahin-Tóth
Jan 21, 2019·Gastroenterology·Julia MayerleMiklós Sahin-Tóth
Nov 25, 2021·International Journal of Cancer. Journal International Du Cancer·Makoto KawamotoMichael Goggins

❮ Previous
Next ❯

Related Concepts

Related Feeds

Birth Defects

Birth defects encompass structural and functional alterations that occur during embryonic or fetal development and are present since birth. The cause may be genetic, environmental or unknown and can result in physical and/or mental impairment. Here is the latest research on birth defects.