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Apoptosis-associated speck-like protein containing a CARD (ASC) expression profiles in familial Mediterranean fever
S Nalbantoglu1, B Tanyolac, A Berdeli
1Faculty of Medicine, Children's Hospital, Molecular Medicine Laboratory, Ege University, Bornova, Izmir, Turkey. nalbantoglusinem@gmail.com
Objectives:
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).
Conclusion:
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.
Insights
Familial Mediterranean Fever (FMF) patients with MEFV mutations show increased ASC mRNA expression, regardless of mutation type. This suggests a link between mutant MEFV/pyrin and ASC up-regulation in FMF inflammation.
Area of Science:
- Immunology
- Genetics
- Molecular Biology
Background:
- Familial Mediterranean Fever (FMF) is a common autoinflammatory disorder linked to the inflammasome pathway.
- Pyrin, encoded by the MEFV gene, interacts with ASC/PYCARD, an inflammasome adaptor protein.
- Both pyrin and ASC can modulate cellular inflammatory responses.
Purpose of the Study:
- To investigate ASC-induced gene expression profiles in FMF patients.
- To analyze these profiles across different MEFV mutation patterns.
Main Methods:
- Quantitative analysis of ASC gene expression using real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).
- Study included 165 Caucasian patients with diagnosed FMF.
Main Results:
- ASC mRNA expression was significantly higher in MEFV mutation-positive patients compared to mutation-negative controls (p = 0.001).
- Increased ASC expression was observed across various MEFV mutation groups (M694V homozygous, heterozygous, compound heterozygous, R202Q/P369S/R408Q).
- No significant differences in ASC mRNA levels were found among the different MEFV mutation-positive groups.
Conclusions:
- ASC mRNA expression is up-regulated in FMF patients with MEFV mutations, irrespective of the specific mutation.
- No significant correlation was identified between specific MEFV genotypes and ASC expression levels.
- Findings suggest a significant association between mutant MEFV/pyrin and elevated ASC expression in FMF pathogenesis.
