Genetic analysis of the STIM1 gene in chronic pancreatitis - Archive ouverte HAL Access content directly
Preprints, Working Papers, ... Year : 2019

Genetic analysis of the STIM1 gene in chronic pancreatitis

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Emmanuelle Masson
  • Function : Author
Wen-Bin Zou
  • Function : Author
Claudia Ruffert
  • Function : Author
Vanessa Holste
  • Function : Author
Patrick Michl
  • Function : Author
Joachim Mössner
  • Function : Author
Maren Ewers
  • Function : Author
Helmut Laumen
  • Function : Author
Hao Wu
  • Function : Author
Dai-Zhan Zhou
  • Function : Author
Zhao-Shen Li
  • Function : Author
Dong Yu
  • Function : Author
Cédric Le Maréchal
  • Function : Author
David Cooper
  • Function : Author
Jian-Min Chen
  • Function : Author
Heiko Witt
  • Function : Author
Jonas Rosendahl
  • Function : Author
Zhuan Liao
  • Function : Author
Claude Férec
  • Function : Author

Abstract

ABSTRACT Chronic pancreatitis is a complex disease that involves many factors, both genetic and environmental. Over the past two decades, molecular genetic analysis of five genes that are highly expressed in human pancreatic acinar cells, namely PRSS1, PRSS2, SPINK1, CTRC and CTRB1 / CTRB2 , has established that a trypsin-dependent pathway plays a key role in the etiology of chronic pancreatitis. Since Ca 2+ deregulation can lead to intracellular trypsin activation in experimental acute pancreatitis, we analyzed STIM1 (encoding stromal interaction molecule-1, the main regulator of Ca 2+ homeostasis in pancreatic acinar cells) as a candidate modifier gene in French, German and Chinese patients with chronic pancreatitis. The French and German subjects were analyzed by Sanger sequencing whereas the Chinese subjects were analyzed by targeted next-generation sequencing confirmed by Sanger sequencing. A total of 37 rare coding variants (35 missense and 2 nonsense) were identified, which were enriched in patients as compared with controls [2.28% (47/2,057) vs. 0.99% (33/3,322); odds ratio = 2.33, P = 0.0001]. This is the first large case-control study to demonstrate a putative association of rare STIM1 coding variants with chronic pancreatitis. Functional analysis will be required to clarify whether or not the rare STIM1 variants detected predispose to pancreatitis.
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Dates and versions

hal-03811468 , version 1 (11-10-2022)

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Emmanuelle Masson, Wen-Bin Zou, Claudia Ruffert, Vanessa Holste, Patrick Michl, et al.. Genetic analysis of the STIM1 gene in chronic pancreatitis. 2022. ⟨hal-03811468⟩
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