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