Original Contribution
The American Journal of Gastroenterology (2005) 100, 338–343; doi:10.1111/j.1572-0241.2005.40810.x
The Familial Mediterranean Fever (MEVF) Gene as a Modifier of Crohn's Disease
Herma Fidder MD1, Yehuda Chowers MD1, Zvi Ackerman MD1, Rivka Dresner Pollak MD1, J Bart A Crusius PhD1, Avi Livneh MD1, Simon Bar-Meir MD1, Benjamin Avidan MD1 and Yael Shinhar PhD1
1Department of Gastroenterology and The Heller Institute of Medical Research, Chaim Sheba Medical Center, Tel Hashomer; the Department of Medicine, Hadassah University Hospital, Jerusalem, Israel; and Laboratory of Immunogenetics, VU University Medical Center, Amsterdam, The Netherlands
Correspondence: Herma Fidder, Department of Gasteroenterology, Hadassah University Hospital, Jerusalem, Israel
Received 6 August 2004; Revised 0000; Accepted 10 August 2004.
Abstract
OBJECTIVES:
Crohn's disease (CD) has been reported to be more frequent among non-Ashkenazi Jewish patients suffering from familial Mediterranean fever (FMF). Interestingly, functional similarities between the CD susceptibility gene (NOD2/CARD15) and the FMF gene (MEFV) have been described: both belong to the death domain containing protein family, important in the regulation of apoptosis, cytokine processing and inflammation.
AIMS:
To investigate the prevalence of MEFV mutations in Jewish non-Ashkenazi CD patients and its putative effect on CD presentation.
METHODS:
Germline DNA of 105 Israeli CD patients of non-Ashkenazi and mixed Ashkenazi–non-Ashkenazi ethnic background was analyzed for three most common MEFV mutations: M694V, V726A, and E148Q. Five patients (4.7%) with a clinical diagnosis of FMF were included. Data obtained from each patient included: age of onset, disease location, and behavior, the presence of extraintestinal manifestations of CD and therapeutic regimens.
RESULTS:
The overall prevalence of mutation carriers among non-FMF-CD patients was 13% (13/100). A stricturing disease pattern was observed in 56% (10/18) of all carriers, FMF-CD, and non-FMF-CD patients, and in 25% (22/87) of noncarriers (OR: 3.7, 95% CI: 1.3–10.5, p= 0.015). The prevalence of fistulas was comparable in both groups. Extraintestinal manifestations were significantly more frequent among carriers than noncarriers (65%vs 32%, OR 3.9, 95% CI = 1.3–11.5, p= 0.015). No differences were observed in disease location and disease severity.
CONCLUSIONS:
MEFV mutations are not associated with CD susceptibility, yet the presence of these mutations appears to be associated with a stricturing disease pattern and extraintestinal disease manifestations of CD.
