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Single Nucleotide Polymorphisms of the MEFV Gene E148Q Are Highly Associated With Disease Phenotype in Crohn's

Satoshi Yamada1, Yusuke Honzawa2, Shuji Yamamoto1

  • 1Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Inflammatory Bowel Diseases
|November 11, 2023
PubMed
Abstract

Insights

Single nucleotide polymorphisms (SNPs) in the MEFV gene, particularly E148Q, are linked to Crohn's disease (CD) behavior. This SNP enhances IL-1β and IL-18 production, potentially driving fibrostenosis in CD patients.

Area of Science:

  • Genetics and Molecular Biology
  • Gastroenterology
  • Immunology

Background:

  • Single nucleotide polymorphisms (SNPs) in the MEFV gene are investigated for their potential role in modifying inflammatory bowel disease (IBD) activity.
  • The prevalence and specific contribution of MEFV gene SNPs to IBD pathophysiology remain largely undetermined.

Purpose of the Study:

  • To analyze the prevalence of 12 MEFV gene SNPs in Japanese IBD patients.
  • To evaluate the association of these SNPs with IBD disease characteristics.
  • To investigate the impact of the E148Q SNP on inflammasome activity and cytokine production in Crohn's disease (CD).

Main Methods:

  • Polymerase chain reaction and next-generation DNA sequencing were used to analyze 12 MEFV gene SNPs in peripheral leukocytes of 69 CD and 32 ulcerative colitis patients.
  • Inflammasome activity, IL-1β, and IL-18 production were assessed in lipopolysaccharide/adenosine triphosphate-stimulated peripheral blood mononuclear cells from CD patients with and without the E148Q SNP.
  • COL1A1 and HSP47 gene expression was analyzed in CCD-18Co cells co-stimulated with IL-1β and other inflammatory cytokines.

Main Results:

  • MEFV gene SNP prevalence in IBD patients mirrored general population databases, with E148Q being the most common.
  • CD patients with the E148Q SNP showed a higher frequency of the stricture phenotype and significantly elevated IL-1β, IL-18 levels, and caspase-1 activity in their peripheral blood mononuclear cells.
  • IL-1β and IL-17A synergistically upregulated COL1A1 and HSP47 gene expression in myofibroblasts.

Conclusions:

  • MEFV gene SNPs, specifically E148Q, appear to influence Crohn's disease behavior.
  • The E148Q SNP is associated with enhanced caspase-1 activity in monocytes, leading to increased IL-1β and IL-18 production in CD patients.
  • IL-1β, in conjunction with IL-17A, promotes the expression of fibrosis-related genes, suggesting E148Q as a potential disease-modifying gene for fibrostenosis in CD.
Keywords:
MEFV geneIL-1βinflammatory bowel disease

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