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The Effect of Renin Angiotensin System Genetic Variants in Acute Pancreatitis

Skipworth, JRA; Nijmeijer, RM; van Santvoort, HC; Besselink, MGH; Schulz, H-U; Kivimaki, M; Kumari, M; ... Montgomery, HE; + view all (2015) The Effect of Renin Angiotensin System Genetic Variants in Acute Pancreatitis. Annals of Surgery , 261 (1) pp. 180-188. 10.1097/SLA.0000000000000655. Green open access

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Abstract

Objectives: We sought association of genetic variants in the renin-angiotensin system (RAS) and vitamin D system with acute pancreatitis (AP) development and severity. Background: The 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. Methods: Five 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. Results: The 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). Conclusions: The 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.

Type: Article
Title: The Effect of Renin Angiotensin System Genetic Variants in Acute Pancreatitis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1097/SLA.0000000000000655
Publisher version: http://doi.org/10.1097/SLA.0000000000000655
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Pancreatitis; RAS; ACE; Genetics
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Internal Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Cardiovascular Science > Centre for Cardiovascular Genetics
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Epidemiology and Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute of Epidemiology and Health > Epidemiology and Public Health
URI: http://discovery.ucl.ac.uk/id/eprint/1427343
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