PHILADELPHIA — More than half of patients with Crohn's disease who required an ileocolic resection carried at least one mutation in a gene known as NOD2, according to a pilot study of 50 patients.
The 52% prevalence of one or more NOD2 mutations in patients who needed surgery contrasts with the 10%–35% prevalence of NOD2 mutations in all Crohn's disease patients previously reported to have had NOD2 testing. This finding suggests NOD2 mutations predispose these patients to a more severe disease that requires surgical management, Lisa S. Poritz, M.D., said at the annual meeting of the American Society of Colon and Rectal Surgeons.
The apparent link between mutations in the NOD2 gene and more severe Crohn's disease is unexpected because people with these mutations have reduced levels of nuclear factor (NF) kappa B, a transcription factor that raises levels of cytokines and other molecules that enhance immune responses. Results from other studies had indicated that levels of NF kappa B are higher in patients with Crohn's disease, and hence NOD2 gene mutations were expected to reduce NF kappa B levels and produce less severe forms of Crohn's disease.
The study involved screening for NOD2 mutations in blood samples from all patients who underwent ileocolic resections for Crohn's disease at the Milton S. Hershey Medical Center in Hershey, Pa., during 1992–2004; so far, tests have been completed on the first 50 of these patients.
NOD2 mutations were found in 26 of the 50 patients (52%), Dr. Poritz said. When the clinical characteristics of patients with NOD2 mutations were compared with those of the 24 patients without mutations, there was no significant difference in the age of Crohn's disease onset, time to first surgery, or percentage of patients needing more than one abdominal surgical procedure. The findings suggest NOD2 mutations do not affect the incidence of recurrent Crohn's disease after ileocolic resection, said Dr. Poritz, chief of colon and rectal surgery research at the Hershey Medical Center.