Publication type
Journal Article
Authors
Publication date
January 15, 2015
Summary:
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.
(C) 2014 by Lippincott Williams & Wilkins.
Published in
Annals of Surgery
Volume and page numbers
Volume: 261 , p.180 -188
DOI
http://dx.doi.org/10.1097/SLA.0000000000000655
ISSN
34932
Subjects
Notes
Not held in Research Library - bibliographic reference only
#522604