eprintid: 1427343
rev_number: 66
eprint_status: archive
userid: 608
dir: disk0/01/42/73/43
datestamp: 2014-04-21 18:50:38
lastmod: 2021-12-01 23:32:46
status_changed: 2018-03-12 13:20:53
type: article
metadata_visibility: show
item_issues_count: 0
creators_name: Skipworth, JRA
creators_name: Nijmeijer, RM
creators_name: van Santvoort, HC
creators_name: Besselink, MGH
creators_name: Schulz, H-U
creators_name: Kivimaki, M
creators_name: Kumari, M
creators_name: Cooper, JA
creators_name: Acharya, J
creators_name: Shankar, A
creators_name: Malago, M
creators_name: Humphries, SE
creators_name: Damink, SWMO
creators_name: Montgomery, HE
title: The Effect of Renin Angiotensin System Genetic Variants in Acute Pancreatitis
ispublished: pub
divisions: UCL
divisions: B02
divisions: C10
divisions: D17
divisions: G94
divisions: D14
divisions: D12
divisions: G19
keywords: Pancreatitis; RAS; ACE; Genetics
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
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.
date: 2015-01-01
date_type: published
publisher: LIPPINCOTT WILLIAMS & WILKINS
official_url: http://doi.org/10.1097/SLA.0000000000000655
vfaculties: VGHCSCI
vfaculties: VFPHS
vfaculties: VFPHS
oa_status: green
full_text_type: other
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_source: PubMed
elements_id: 941787
doi: 10.1097/SLA.0000000000000655
lyricists_name: Acharya, Jayshree
lyricists_name: Cooper, Jacqueline
lyricists_name: Humphries, Stephen
lyricists_name: Kivimaki, Mika
lyricists_name: Kumari, Meena
lyricists_name: Montgomery, Hugh
lyricists_id: JACHA04
lyricists_id: JCOOP43
lyricists_id: SEHUM16
lyricists_id: MJKIV95
lyricists_id: MKUMA95
lyricists_id: HEMON01
actors_name: Waragoda Vitharana, Nimal
actors_id: NWARR44
actors_role: owner
full_text_status: public
publication: Annals of Surgery
volume: 261
number: 1
pagerange: 180-188
pages: 9
issn: 1528-1140
citation:        Skipworth, JRA;    Nijmeijer, RM;    van Santvoort, HC;    Besselink, MGH;    Schulz, H-U;    Kivimaki, M;    Kumari, M;                             ... Montgomery, HE; + view all <#>        Skipworth, JRA;  Nijmeijer, RM;  van Santvoort, HC;  Besselink, MGH;  Schulz, H-U;  Kivimaki, M;  Kumari, M;  Cooper, JA;  Acharya, J;  Shankar, A;  Malago, M;  Humphries, SE;  Damink, SWMO;  Montgomery, HE;   - view fewer <#>    (2015)    The Effect of Renin Angiotensin System Genetic Variants in Acute Pancreatitis.                   Annals of Surgery , 261  (1)   pp. 180-188.    10.1097/SLA.0000000000000655 <https://doi.org/10.1097/SLA.0000000000000655>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/1427343/1/Acharya_Pancreatitis%20published.pdf