An integrated picture of chronic pancreatitis derived by mapping variants in multiple disease genes onto pathogenic pathways

Prasad, H and Shah, IA and Kurien, RT and Chowdhury, SD and Visweswariah, SS (2024) An integrated picture of chronic pancreatitis derived by mapping variants in multiple disease genes onto pathogenic pathways. In: Human Molecular Genetics, 33 (21). pp. 1887-1889.

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Abstract

Chronic pancreatitis (CP) is an etiologically and genetically heterogeneous inflammatory syndrome characterised by progressive damage to the exocrine and endocrine components of the pancreas 1. The multigenic paradigm of CP has sparked research in recent years 2. We aimed to expand the current knowledge of genetic susceptibility of pancreatitis in patients of Indian origin. By employing whole-exome sequencing in an Indian hospital cohort, we dissect the genetic landscape associated with CP or recurrent acute pancreatitis (RAP). Notably, all patients had at least one genetic variant identified in a pancreatitis-risk gene, and most had a co-occurrence of a second variant in an additional risk gene. Based on the presence of both acinar and ductal gene variants in individual patients, we propose a two-hit hypothesis where variants in proteins expressed in both acinar and ductal cells are critical for RAP/CP development. © 2024 The Author(s). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Item Type:	Journal Article
Publication:	Human Molecular Genetics
Publisher:	Oxford University Press
Additional Information:	The copyright for this article belongs to the Publisher.
Keywords:	cystic fibrosis transmembrane conductance regulator, acinar cell; Article; chronic pancreatitis; clinical article; cohort analysis; gene mapping; genetic risk; genetic susceptibility; genetic variability; genotype; human; Indian; knowledge; phenotype; protein expression; recurrent disease; whole exome sequencing; adult; female; genetic predisposition; genetic variation; genetics; India; male; metabolism; middle aged; pathology; whole exome sequencing, Acinar Cells; Adult; Exome Sequencing; Female; Genetic Predisposition to Disease; Genetic Variation; Humans; India; Male; Middle Aged; Pancreatitis, Chronic
Department/Centre:	Others
Date Deposited:	29 Nov 2024 08:51
Last Modified:	29 Nov 2024 08:51
URI:	http://eprints.iisc.ac.in/id/eprint/86947

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