title: Apoptosis-associated speck-like protein containing a CARD (ASC) expression profiles in familial Mediterranean fever (FMF) patients with different MEFV mutation patterns.
abstract: OBJECTIVE
  The inflammasome complex and the inflammatory pathway have been implicated in the pathogenesis of the most common autoinflammatory disorder, familial Mediterranean fever (FMF). Pyrin, the protein product of the FMF gene MEFV, interacts with the inflammasome complex adaptor protein ASC/PYCARD (apoptosis-associated speck-like protein with a CARD). Pyrin and ASC can both function as either inducers or suppressors of the cellular inflammatory response. We aimed to characterize ASC-induced gene expression profiles in FMF patients with different MEFV mutation patterns.
  
  
  METHODS
  A total of 165 Caucasian patients with clinical and molecular FMF diagnoses were enrolled in the study. ASC gene expression was quantified by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).
  
  
  RESULTS
  ASC mRNA expression was increased in the MEFV mutation-positive group compared to the mutation-negative group (p = 0.001). The fold changes of ASC expression in the M694V homozygous (p = 0.02), M694V heterozygous (p = 0.012), compound heterozygous (p = 0.002), and R202Q/P369S/R408Q (p = 0.00) groups relative to the MEFV mutation-negative group were +2.4, +2.7, +3, and +3.4, respectively. qRT-PCR did not reveal a significant difference in ASC mRNA expression levels among the MEFV mutation-positive groups (p > 0.05).
  
  
  CONCLUSIONS
  ASC mRNA expression was up-regulated in patients carrying MEFV mutations independent of mutation type. There was no significant relationship between specific MEFV genotypes and the level of ASC expression in the patient group analysed. Thus, the findings of this work may suggest a crucial relationship between mutant MEFV/pyrin and remarkable ASC up-regulation in FMF inflammation.
authors.affiliation: Faculty of Medicine, Children's Hospital, Molecular Medicine Laboratory, Ege University, Bornova, Izmir, Turkey. nalbantoglusinem@gmail.com
authors.forename: S
authors.initials: S
authors.lastname: Nalbantoglu
authors.forename: B
authors.initials: B
authors.lastname: Tanyolac
authors.forename: A
authors.initials: A
authors.lastname: Berdeli
mesh_terms: D000293:Adolescent; D000328:Adult; D053468:CARD Signaling Adaptor Proteins; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins / Q000235:genetics*; D010505:Familial Mediterranean Fever / Q000235:genetics* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D000071198:Pyrin; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D053468:CARD Signaling Adaptor Proteins; D003598:Cytoskeletal Proteins; C000604192:MEFV protein, human; C402202:PYCARD protein, human; D000071198:Pyrin; D012333:RNA, Messenger