Genetic predisposition to thrombophilia in inflammatory bowel disease

J Clin Gastroenterol. 2011 Mar;45(3):e25-9. doi: 10.1097/MCG.0b013e3181eb6132.

Abstract

Background: Inflammatory bowel disease (IBD) is linked to a definite risk of thromboembolic events (TE), but data on the role of prothrombotic genetic mutations are conflicting.

Study: Fourteen genetic factors involved in TE pathogenesis were investigated in a homogeneous cohort of Sicilian patients with IBD with and without history of TE and in healthy controls. Forty IBD patients (21 CD, 19 UC) and 20 healthy individuals were enrolled. Genetic testing was based on the reverse hybridization principle by a commercial assay that analyzes 14 polymorphisms involved in thrombophilia and cholesterol metabolism. The rate of genetic polymorphisms and mutations was compared between IBD patients and healthy controls.

Results: No significant difference in allelic frequency was found between IBD patients and controls except AGT T/T, though a trend toward significance was found also for ACE D/D. Eight out of 9 patients with earlier history of TE had more than 1 polymorphism, compared with 12 out of 31 without TE. In patients with IBD the mutation AGT T/T was related to male sex (P<0.0259) and, marginally, to arterial hypertension (P<0.06) and diabetes (P<0.09).

Conclusions: Our data confirm a definite risk of TE in IBD (22.5% of our series). An increased frequency of the genotypes ACE D/D and AGT T/T, never reported so far, was found. In IBD patients TE has a multifactorial genesis with involvement of several genes as well and acquired factors. Genetic screening for prothrombotic factors could help segregate IBD patients at higher risk of TE.

MeSH terms

  • Adult
  • Aged
  • Angiotensinogen / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Inflammatory Bowel Diseases / complications*
  • Male
  • Middle Aged
  • Mutation
  • Peptidyl-Dipeptidase A / genetics
  • Polymorphism, Genetic
  • Risk Factors
  • Sicily
  • Thrombophilia / etiology
  • Thrombophilia / genetics*

Substances

  • AGT protein, human
  • Angiotensinogen
  • ACE protein, human
  • Peptidyl-Dipeptidase A