Association between reduced levels of MEFV messenger RNA in peripheral blood leukocytes and acute inflammation.
OBJECTIVE
Familial Mediterranean fever (FMF) is associated with more than 70 missense mutations in the MEFV gene. The purpose of this study was to investigate the relative expression of messenger RNA (mRNA) for the MEFV gene in peripheral blood leukocytes (PBLs) obtained from patients with FMF during attacks of acute abdominal inflammation as well as during asymptomatic periods.


METHODS
We studied 16 patients with FMF during an attack of acute peritonitis and 17 otherwise healthy individuals who were undergoing surgery because of acute appendicitis. Blood samples were collected from both groups of patients during both acute inflammatory and asymptomatic periods. Relative levels of MEFV mRNA in PBLs were detected with real-time reverse transcriptase-polymerase chain reaction using LightCycler, with 2 sets of primers for the MEFV gene (exons 7-10 and exons 2-3) and with primers for CIAS1 and PSTPIP1 genes. Expression levels were compared with beta(2)-microglobulin as an internal control.


RESULTS
MEFV expression was reduced in FMF patients during asymptomatic periods as compared with the non-FMF controls (P < 0.001). We observed a further decrease in MEFV expression in FMF patients during periods of inflammation (P = 0.01). Reduced levels of MEFV mRNA were also noted during the preoperative period as compared with asymptomatic periods in control patients with acute appendicitis (P = 0.01). CIAS1 expression in PBLs from patients with FMF was also found to be lower than that in the control patients. However, CIAS1 expression did not change with acute inflammation.


CONCLUSIONS
This study confirmed that reduced expression of the MEFV gene is associated with inflammation and that it may be one of the pathogenic mechanisms of the attacks of inflammation in FMF patients, along with disease-associated variations in pyrin.
Ustek
Duran
D
Istanbul University, Institute for Experimental Medical Research, Istanbul, Turkey.
Ekmekci
Cumhur Gökhan
CG
Selçukbiricik
Fatih
F
Cakiris
Aris
A
Oku
Basar
B
Vural
Burcak
B
Yanar
Hakan
H
Taviloglu
Korhan
K
Ozbek
Ugur
U
Gül
Ahmet
A
D000208:Acute Disease; D000328:Adult; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D010505:Familial Mediterranean Fever / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010538:Peritonitis / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D000071198:Pyrin; D012333:RNA, Messenger / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; D000071198:Pyrin; D012333:RNA, Messenger