The effect of renin angiotensin system genetic variants in acute pancreatitis.

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.

journal_name

Ann Surg

journal_title

Annals of surgery

authors

Skipworth JR,Nijmeijer RM,van Santvoort HC,Besselink MG,Schulz HU,Kivimaki M,Kumari M,Cooper JA,Acharya J,Shankar A,Malago M,Humphries SE,Olde Damink SW,Montgomery HE

doi

10.1097/SLA.0000000000000655

subject

Has Abstract

pub_date

2015-01-01 00:00:00

pages

180-8

issue

1

eissn

0003-4932

issn

1528-1140

journal_volume

261

pub_type

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