Leiden mutation in patients with Crohn's disease

Inherited resistance to activated protein C is a common risk factor of venous thrombosis. In a majority of patients the defect is caused by single-point mutation in the gene for factor V. This mutated form of factor Va is more stable against proteolytic attack by activated protein C. The prevalence of this inherited defect in the European population is at least 5%. The risk of thrombosis is increased in the case of heterozygosity 5- to 10-fold, in homozygous subjects 50- to 100-fold, but even homozygous individuals will not necessarily suffer from thrombosis. The aim of our study was to determine whether the presence of Leiden mutation might play a role in the pathophysiology and clinical manifestation of Crohn's disease.

Thirty-four patients with Crohn's disease (mean age 34 years, range 21-72 years) were studied. None of them had a history of thrombotic episodes. We examined the case history for risk factors: use of oral contraceptive, steroids, cigarette smoking. Levels of fibrinogen, APTT, lupus anticoagulant and levels of IgG and IgM class anticardiolipin (ACL) antibodies were determined. The Leiden mutation was detected by PCR method (Denninger et al., 1995).

Fibrinogen was elevated in five cases, lupus anticoagulant in one case, but none of the patients had ACL antibodies in the serum. Molecular analyses showed heterozygosity for the Leiden factor V gene mutation in the case of 30 patients (25%).

Thromboembolic events frequently complicate the clinical course of patients with Crohn's disease; however, we do not have enough knowledge about its role in manifestation of the disease. These results suggested the high frequency of Leiden mutation among our patients and suggest a new genetic background of Crohn's disease.