Association analysis of genetic variants in the myosin IXB gene in acute pancreatitis

PLoS One. 2013 Dec 30;8(12):e85870. doi: 10.1371/journal.pone.0085870. eCollection 2013.

Abstract

Introduction: 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.

Conclusion: Variants in MYO9B may be involved in acute pancreatitis, but we found no evidence for involvement of PARD3 or MAGI2.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Carrier Proteins / genetics
  • Cell Cycle Proteins / genetics
  • Cohort Studies
  • Female
  • Germany
  • Guanylate Kinases
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Myosins / genetics*
  • Netherlands
  • Pancreatitis / genetics*
  • Polymorphism, Single Nucleotide*

Substances

  • Adaptor Proteins, Signal Transducing
  • Carrier Proteins
  • Cell Cycle Proteins
  • Membrane Proteins
  • PARD3 protein, human
  • myosin IXB
  • Guanylate Kinases
  • MAGI2 protein, human
  • Myosins

Grants and funding

This study was supported by Senter, an agency of the Dutch Ministry of Economic Affairs (grant. no. TSGE3109). RMN was supported by an Alexandre Suerman stipend from the University Medical Center Utrecht. JTJV was supported by a grant from the Dutch Diabetes Foundation (2007.00.069). CW was supported by a VICI grant (918.66.620) from the Netherlands Organization for Scientific Research. The study was further supported by the Deutsche Krebshilfe/Dr. Mildred-Scheel-Stiftung (109102), the Deutsche Forschungsgemeinschaft (DFG GRK840-E3/E4, MA 4115/1-2/3, NI 1297/1-1), the German Federal Ministry of Education and Research (BMBF GANI-MED 03152061A and BMBF 0314107) and the European Union (EU-FP-7: EPC-TM and EU-FP7-REGPOT-2010-1). All funding was independent of the work described in this article. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.