The possession of exon 2 or exon 3 variants in the MEFV gene promotes inflammasome activation in Japanese patients with familial Mediterranean fever with a heterozygous exon 10 mutation.

Abstract

OBJECTIVES:

The modification and pathogenesis of MEFV exon 2 or 3 variants in familial Mediterranean fever (FMF) remains unclear. We compared the clinical and laboratory characteristics between the coexistence and noncoexistence of MEFV exon 2 or 3 variants in patients with FMF that had a heterozygous MEFV exon 10 mutation.

METHODS:

We excluded patients with FMF that had two MEFV exon 10 mutations in one or more alleles and/or MEFV mutations in exons other than in exons 2, 3, or 10. Finally, we reviewed 131 Japanese patients with FMF that had a heterozygous MEFV exon 10 mutation, and they were divided into the groups with and without MEFV exon 2 or 3 variants of 97 and 34, respectively.

RESULTS:

All patients with MEFV exon 2 variants had either E148Q and/or L110P variants, none of patients had exon 3 variants. In the univariate analysis, the group with variants had significantly earlier onset, a higher percentage of thoracic pain with febrile attacks, a higher frequency of attack, and a higher IL-18 level at remission compared to the group without variants (all, p<0.05). Importantly, multivariate analyses showed that the coexistence of MEFV exon 2 variants was independently and significantly associated with earlier onset of FMF and thoracic pain (both, p<0.05).

CONCLUSIONS:

Our results suggested that coexistence of MEFV exon 2 variants have additional effects on manifestations of FMF with MEFV exon 10 mutations. Our findings highlighted the modifications and pathogenesis of such MEFV variants in FMF.

• Authors: Yushiro Endo, Tomohiro Koga, Kazusato Hara, Kaori Furukawa, Kazunaga Agematsu, Akihiro Yachie, Junya Masumoto, Kiyoshi Migita, Atsushi Kawakami
• Journal: Clinical and experimental rheumatology (Clin Exp Rheumatol) 2020 Sep-Oct Vol. 38 Suppl 127 Issue 5 Pg. 49-52 ISSN: 0392-856X [Print] Italy
• PMID: 33331265 (Publication Type: Journal Article)

Chemical References

• Inflammasomes
• MEFV protein, human
• Pyrin

Topics

• Exons
• Familial Mediterranean Fever (diagnosis, genetics)
• Humans
• Inflammasomes
• Japan
• Mutation
• Pyrin (genetics)