The familial Mediterranean fever (MEVF) gene as a modifier of Crohn's disease.
OBJECTIVE
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.


OBJECTIVE
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.
Fidder
Herma
H
Department of Gastroenterology and The Heller Institute of Medical Research, Chaim Sheba Medical Center, Tel Hashomer, Israel.
Chowers
Yehuda
Y
Ackerman
Zvi
Z
Pollak
Rivka Dresner
RD
Crusius
J Bart A
JB
Livneh
Avi
A
Bar-Meir
Simon
S
Avidan
Benjamin
B
Shinhar
Yael
Y
D000328:Adult; D003424:Crohn Disease / Q000150:complications / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D003598:Cytoskeletal Proteins; D010505:Familial Mediterranean Fever / Q000150:complications / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D007585:Jews; D008297:Male; D009154:Mutation; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D000071198:Pyrin
D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D011506:Proteins; D000071198:Pyrin