title: The effect of renin angiotensin system genetic variants in acute pancreatitis.
abstract: OBJECTIVE
  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.
authors.affiliation: *Department of Surgery and Interventional Science, University College London, London, United Kingdom †Department of Hepatopancreaticobiliary Surgery, Royal Free Hospital NHS Trust, London, United Kingdom ‡UCL Institute of Human Health & Performance, University College London, London, United Kingdom §Department of Internal Medicine, Rijnstate Hospital, Arnhem, The Netherlands ¶Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands ∥Department of Surgery, G4-196, AMC Amsterdam, Amsterdam, The Netherlands **General Surgery Department, Medical Faculty of Otto-von-Guericke University, Magdeburg, Germany ††Department of Epidemiology and Public Health, University College London, London, United Kingdom ‡‡Centre for Cardiovascular Genetics, University College London, London, United Kingdom §§Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
authors.forename: James R A
authors.initials: JR
authors.lastname: Skipworth
authors.forename: Rian M
authors.initials: RM
authors.lastname: Nijmeijer
authors.forename: Hjalmar C
authors.initials: HC
authors.lastname: van Santvoort
authors.forename: Marc G H
authors.initials: MG
authors.lastname: Besselink
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Schulz
authors.forename: Mika
authors.initials: M
authors.lastname: Kivimaki
authors.forename: Meena
authors.initials: M
authors.lastname: Kumari
authors.forename: Jackie A
authors.initials: JA
authors.lastname: Cooper
authors.forename: Jay
authors.initials: J
authors.lastname: Acharya
authors.forename: Arjun
authors.initials: A
authors.lastname: Shankar
authors.forename: Massimo
authors.initials: M
authors.lastname: Malago
authors.forename: Steve E
authors.initials: SE
authors.lastname: Humphries
authors.forename: Steven W M
authors.initials: SW
authors.lastname: Olde Damink
authors.forename: Hugh E
authors.initials: HE
authors.lastname: Montgomery
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010195:Pancreatitis / Q000235:genetics*; D019512:Pancreatitis, Alcoholic / Q000235:genetics; D007703:Peptidyl-Dipeptidase A / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012083:Renin / Q000235:genetics; D012084:Renin-Angiotensin System / Q000235:genetics*; D014807:Vitamin D / Q000235:genetics*; D055815:Young Adult
chemical_list: D014807:Vitamin D; D007703:Peptidyl-Dipeptidase A; D012083:Renin
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