• James R A Skipworth, Rian M Nijmeijer, Hjalmar C van Santvoort, Marc G H Besselink, Hans-Ulrich Schulz, Mika Kivimaki, Meena Kumari, Jackie A Cooper, Jay Acharya, Arjun Shankar, Massimo Malago, Steve E Humphries, Steven W M Olde Damink, and Hugh E Montgomery.
• *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.
• Ann. Surg. 2015 Jan 1; 261 (1): 180-8.

ObjectivesWe sought association of genetic variants in the renin-angiotensin system (RAS) and vitamin D system with acute pancreatitis (AP) development and severity.BackgroundThe endocrine RAS is involved in circulatory homeostasis through the pressor action of angiotensin II at its AT1 receptor. However, local RAS regulate growth and inflammation in diverse cells and tissues, and their activity may be suppressed by vitamin D. Intrapancreatic angiotensin II generation has been implicated in the development of AP.MethodsFive hundred forty-four white patients with AP from 3 countries (United Kingdom, 22; Germany, 136; and The Netherlands 386) and 8487 control subjects (United Kingdom 7833, The Netherlands 717) were genotyped for 8 polymorphisms of the RAS/vitamin D systems, chosen on the basis of likely functionality.ResultsThe angiotensin-converting enzyme I (rather than D) allele was significantly associated with alcohol-related AP when all cohorts were combined (P = 0.03). The renin rs5707 G (rather than A) allele was associated with AP (P = 0.002), infected necrosis (P = 0.025) and mortality (P = 0.046).ConclusionsThe association of 2 RAS polymorphisms with AP suggests the need for further detailed analysis of the role of RAS/vitamin D in the genesis or severity of AP, particularly given the ready potential for pharmacological manipulation of this system using existing marketed agents. However, further replication studies will be required before any such association is considered robust, particularly given the significant heterogeneity of AP causation and clinical course.

26 keywords...

hide…