Microarray analysis of circulating microRNAs in familial Mediterranean fever.
OBJECTIVE
Familial Mediterranean fever (FMF) is an autoinflammatory disease caused by mutations in MEFV. Mutations in exon 10 are associated with typical FMF phenotypes, whereas the pathogenic role of variants in exons 2 and 3 remains uncertain. Recent evidence suggests that circulating microRNAs (miRNAs) are potentially useful biomarkers in several diseases. Therefore, their expression was assessed in FMF.


METHODS
The subjects were 24 patients with FMF who were between attacks: eight with exon 10 mutations (group A), eight with exon 3 mutations (group B), and eight without exon 3 or 10 mutations (group C). We also investigated eight cases of PFAPA as disease controls. Exosome-rich fractionated RNA was subjected to miRNA profiling by microarray.


RESULTS
Using the expression patterns of 26 miRNAs, we classified FMF (groups A, B, and C) and PFAPA with 78.1% accuracy. In FMF patients, groups A and B, A and C, and B and C were distinguished with 93.8, 87.5, and 100% accuracy using 24, 30, and 25 miRNA expression patterns, respectively.


CONCLUSIONS
These findings suggest that expression patterns of circulating miRNAs differ among FMF subgroups based on MEFV mutations between FMF episodes. These patterns may serve as a useful biomarker for detecting subgroups of FMF.
a Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences , Kanazawa University , Kanazawa , Japan.
Taizo
T
Wada
a Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences , Kanazawa University , Kanazawa , Japan.
Tomoko
T
Toma
a Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences , Kanazawa University , Kanazawa , Japan.
Yusuke
Y
Matsuda
a Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical and Health Sciences , Kanazawa University , Kanazawa , Japan.
Akihiro
A
Yachie
b Department of Hepatology, Graduate School of Medicine , Osaka City University , Osaka , Japan.
Saori
S
Itami
c Department of Physics , Chuo University , Tokyo , Japan.
Y-H
YH
Taguchi
b Department of Hepatology, Graduate School of Medicine , Osaka City University , Osaka , Japan.
Yoshiki
Y
Murakami
D000328:Adult; D015415:Biomarkers / Q000097:blood; D000074166:Circulating MicroRNA / Q000097:blood / Q000235:genetics*; D005091:Exons; D010505:Familial Mediterranean Fever / Q000097:blood / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation
D015415:Biomarkers; D000074166:Circulating MicroRNA
Autoinflammatory disease; MEFV; familial Mediterranean fever; microRNAs