title: Association analysis of genetic variants in the myosin IXB gene in acute pancreatitis.
abstract: BACKGROUND
  Impairment of the mucosal barrier plays an important role in the pathophysiology of acute pancreatitis. The myosin IXB (MYO9B) gene and the two tight-junction adaptor genes, PARD3 and MAGI2, have been linked to gastrointestinal permeability. Common variants of these genes are associated with celiac disease and inflammatory bowel disease, two other conditions in which intestinal permeability plays a role. We investigated genetic variation in MYO9B, PARD3 and MAGI2 for association with acute pancreatitis.
  
  
  METHODS
  Five single nucleotide polymorphisms (SNPs) in MYO9B, two SNPs in PARD3, and three SNPs in MAGI2 were studied in a Dutch cohort of 387 patients with acute pancreatitis and over 800 controls, and in a German cohort of 235 patients and 250 controls.
  
  
  RESULTS
  Association to MYO9B and PARD3 was observed in the Dutch cohort, but only one SNP in MYO9B and one in MAGI2 showed association in the German cohort (p < 0.05). Joint analysis of the combined cohorts showed that, after correcting for multiple testing, only two SNPs in MYO9B remained associated (rs7259292, p = 0.0031, odds ratio (OR) 1.94, 95% confidence interval (95% CI) 1.35-2.78; rs1545620, p = 0.0006, OR 1.33, 95% CI 1.16-1.53). SNP rs1545620 is a non-synonymous SNP previously suspected to impact on ulcerative colitis. None of the SNPs showed association to disease severity or etiology.
  
  
  CONCLUSIONS
  Variants in MYO9B may be involved in acute pancreatitis, but we found no evidence for involvement of PARD3 or MAGI2.
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Rian M
authors.initials: RM
authors.lastname: Nijmeijer
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Hjalmar C
authors.initials: HC
authors.lastname: van Santvoort
authors.affiliation: Complex Genetics Group, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands ; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zhernakova
authors.affiliation: Department of Internal Medicine A, Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Teller
authors.affiliation: Department of Internal Medicine A, Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: Jonas A
authors.initials: JA
authors.lastname: Scheiber
authors.affiliation: Complex Genetics Group, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Carolien G
authors.initials: CG
authors.lastname: de Kovel
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands ; Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Marc G H
authors.initials: MG
authors.lastname: Besselink
authors.affiliation: Department of Cell Biology, Immunology Section, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Jeroen T J
authors.initials: JT
authors.lastname: Visser
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Femke
authors.initials: F
authors.lastname: Lutgendorff
authors.affiliation: Department of Radiology, St Antonius Hospital, Nieuwegein, the Netherlands.
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Bollen
authors.affiliation: Department of Surgery, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Marja A
authors.initials: MA
authors.lastname: Boermeester
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands ; Department of Operating Room/Evidence Based Surgery, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands ; Department of Medical Microbiology and Immunology, St Antonius Hospital, Nieuwegein, the Netherlands.
authors.forename: Ger T
authors.initials: GT
authors.lastname: Rijkers
authors.affiliation: Department of Internal Medicine A, Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: Frank U
authors.initials: FU
authors.lastname: Weiss
authors.affiliation: Department of Internal Medicine A, Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Mayerle
authors.affiliation: Department of Internal Medicine A, Ernst-Moritz-Arndt University, Greifswald, Germany.
authors.forename: Markus M
authors.initials: MM
authors.lastname: Lerch
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands ; Department of Operating Room/Evidence Based Surgery, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Hein G
authors.initials: HG
authors.lastname: Gooszen
authors.affiliation: Department of Surgery, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Louis M A
authors.initials: LM
authors.lastname: Akkermans
authors.affiliation: Complex Genetics Group, Department of Medical Genetics, University Medical Center Utrecht, Utrecht, the Netherlands ; Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
mesh_terms: D000208:Acute Disease; D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D015331:Cohort Studies; D005260:Female; D005858:Germany; D051528:Guanylate Kinases; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009218:Myosins / Q000235:genetics*; D009426:Netherlands; D010195:Pancreatitis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; C509689:PARD3 protein, human; C113469:myosin IXB; D051528:Guanylate Kinases; C485777:MAGI2 protein, human; D009218:Myosins