The Effect of Renin Angiotensin System Genetic Variants in Acute Pancreatitis. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Skipworth, James R. A.; Nijmeijer, Rian M.; van Santvoort, Hjalmar C.; Besselink, Marc G. H.; Schulz, Hans-Ulrich; Kivimaki, Mika; Kumari, Meena; Cooper, Jackie A.; Acharya, Jay; Shankar, Arjun; Malago, Massimo; Humphries, Steve E.; Olde Damink, Steven W. M.; Montgomery, Hugh E.
• Is Part Of: Annals of surgery. Volume 261:Issue 1(2015:Jan.)
• Publication Date: 2015-01
• Subjects: Surgery -- Periodicals; 617.005
• DOI: 10.1097/SLA.0000000000000655
• Languages: English
• ISSNs: 0003-4932

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Objectives:</title> <p>We sought association of genetic variants in the renin-angiotensin system (RAS) and vitamin D system with acute pancreatitis (AP) development and severity.</p> </sec> <sec> <title>Background:</title> <p>The endocrine RAS is involved in circulatory homeostasis through the pressor action of angiotensin II at its AT<sub>1</sub> 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.</p> </sec> <sec> <title>Methods:</title> <p>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.</p> </sec> <sec> <title>Results:</title> <p>The <italic>angiotensin-converting enzyme</italic> I (rather than D) allele was significantly associated with alcohol-related AP when all cohorts were combined (<italic>P</italic> = 0.03). The <italic>renin</italic> rs5707 G (rather than A) allele was associated with AP (<italic>P</italic> = 0.002), infected necrosis (<italic>P</italic> = 0.025) and mortality (<italic>P</italic> = 0.046).</p> </sec> <sec> <title>Conclusions:</title> <p>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.</p> </sec> </abstract>