Impact of Mediterranean Fever Gene Mutations on Clinical Characteristics in Patients With Inflammatory Bowel Disease.

BACKGROUND AND AIMS: The Mediterranean fever (MEFV) gene, which encodes a pyrin protein, is the causative gene of familial Mediterranean fever. Patients with inflammatory bowel disease (IBD) have a significantly higher frequency of MEFV mutations than healthy controls; however, the pathological significance of this difference remains unknown. This study investigated the relationship between MEFV mutations and the clinical characteristics of IBD and refractoriness in patients with a confirmed diagnosis of ulcerative colitis (UC) or Crohn's disease (CD).

METHODS

This retrospective cohort included 260 patients with UC and 131 patients with CD who visited Sapporo Medical University Hospital or Kyorin University Hospital from April 2021 to March 2023. Demographic and clinical data were collected, and blood samples were examined for MEFV mutations using next generation sequencing.

RESULTS

Mutations of the MEFV gene were found in 60.8% of UC and 56.5% of CD patients. Two or more overlapping mutations were identified in 26.2% patients with UC and 19.8% patients with CD. In patients with IBD, mutations in exons 2 and 3 were associated with extraintestinal manifestations (EIMs), and the coexistence of exon 2 and 3 mutations further strengthened this association. G250R (P = .0096, odds ratio 3.49 [1.36-8.98]) and G304R (P = .039, odds ratio 2.62 [1.05-6.54]) in exon 2, and P373Q (P = .0016, odds ratio 7.86 [2.19-28.26]) in exons 3, were significantly associated with EIMs; when stratifying patients with IBD, this trend was observed in patients with UC, but not in those with CD.

CONCLUSION

The MEFV mutation rate was higher in Japanese patients with UC and CD than in healthy controls. MEFV mutations could influence EIMs in patients with IBD.