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The effect of renin angiotensin system genetic variants in acute pancreatitis

James R A Skipworth1, Rian M Nijmeijer, Hjalmar C van Santvoort

  • 1*Department of Surgery and Interventional Science, University College London, London, United Kingdom †Department of Hepatopancreaticobiliary Surgery, Royal Free Hospital NHS Trust, London, United Kingdom ‡UCL Institute of Human Health & Performance, University College London, London, United Kingdom §Department of Internal Medicine, Rijnstate Hospital, Arnhem, The Netherlands ¶Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands ∥Department of Surgery, G4-196, AMC Amsterdam, Amsterdam, The Netherlands **General Surgery Department, Medical Faculty of Otto-von-Guericke University, Magdeburg, Germany ††Department of Epidemiology and Public Health, University College London, London, United Kingdom ‡‡Centre for Cardiovascular Genetics, University College London, London, United Kingdom §§Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.

Annals of Surgery
|April 19, 2014
PubMed
Abstract

Insights

Genetic variants in the renin-angiotensin system (RAS) are linked to acute pancreatitis (AP) development and severity. Specific RAS gene polymorphisms show associations with alcohol-related AP, infected necrosis, and mortality.

Area of Science:

  • Genetics
  • Endocrinology
  • Gastroenterology

Background:

  • The renin-angiotensin system (RAS) regulates circulatory homeostasis and local tissue functions, with potential interaction with vitamin D.
  • Intrapancreatic angiotensin II generation is implicated in acute pancreatitis (AP) pathogenesis.
  • Local RAS activity may be modulated by vitamin D.

Purpose of the Study:

  • To investigate the association between genetic variants in the renin-angiotensin system (RAS) and vitamin D system with the development and severity of acute pancreatitis (AP).

Main Methods:

  • Genotyping of 544 white patients with AP and 8487 control subjects from three countries for 8 polymorphisms in RAS and vitamin D systems.
  • Analysis focused on polymorphisms with presumed functional significance.

Main Results:

  • The angiotensin-converting enzyme I allele was associated with alcohol-related AP (P = 0.03).
  • The renin rs5707 G allele showed association with AP (P = 0.002), infected necrosis (P = 0.025), and mortality (P = 0.046).

Conclusions:

  • Two RAS polymorphisms are associated with AP, suggesting a role for RAS/vitamin D in AP pathogenesis and severity.
  • Further research and replication studies are needed to confirm these findings and explore therapeutic potential.
  • The heterogeneity of AP necessitates careful consideration in future studies.

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