Familial Mediterranean Fever Gene Mutations and Inflammatory Arthritis
Abbas Mirzaei*
Corresponding Author: Abbas Mirzaei, Department of Internal Medicine, Valiasr Hospital, Zanjan University of Medical Sciences, Zanjan, Iran
Received: August 31, 2018; Revised: January 11, 2019; Accepted: September 06, 2018
Citation: Mirzaei A. (2019) Familial Mediterranean Fever Gene Mutations and Inflammatory Arthritis. J Rheumatol Res, 1(1): 1-4.
Copyrights: ©2019 Mirzaei A. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Familial Mediterranean Fever, i.e., FMF, is an acquired hereditary disease that causes repetitive scenes of fever with serosal, cutaneous and fiery joint inflammation that are commonly joined by agony in the stomach area, chest or joints. It regularly happens in people of Mediterranean and Center Eastern plummet and the principal scenes ordinarily start in adolescence.

The unrest has been given diverse names, including familial paroxysmal polyserositis, discontinuous peritonitis, tedious polyserositis, liberal paroxysmal peritonitis, incidental contamination or periodic fever, Reimann irregular infection or Reimann issue, Siegal-Cattan-Mamou illness and Wolff discontinuous disease.


Familial Mediterranean Fever (FMF) is an inherited disease characterized with recurrent episodes of fever with serosal, cutaneous and inflammatory arthritis [1]. One important genetic factor that has been proposed as a candidate gene for the FMF is Mediterranean Fever (MEFV) gene mutation [2,3]. MEFV gene is located on chromosome 16p13 and comprises 10 exons and 781 codons and produces a protein named pyrin or Marenostrin [2,3]. The protein expressed mainly in neutrophils and macrophages and has inhibitory effects on inflammation through leucocyte cytoskeletal organization on polymorphonuclear cells and monocytes and modulates the production of the potent pro-inflammatory cytokine interleukin-1β through regulation of nuclear factor-κB and caspase-1 [4,5]. There are two apparent mutational hot spots: one in exon 2 and the other in exon 10 [3]. Four of five common mutations M694V, V726A, M680I and M694I have been located in exon 10 and one E148Q is identified in exon 2 [3]. According to the literature review MEFV mutations were linked to inflammatory arthritis and also they may have roles in the disease severity [6-9]. Most of these literatures conducted in areas with high prevalence of FMF and they investigated the mutation rate of MEFV genes in patients with ankylosing spondylitis (AS). All of them showed the increased overall mutation rate of MEFV gene in patients with AS [6,10-17]. However, the influence to the prognosis is less likely [10,16]. The M694V mutation was the most common mutation supposed to be associated with sacroiliitis as a predominant feature of AS [11-15,17]. Table 1 presents the studies conducted on patients with AS.

According to the studies mentioned in Table 1, there is an association between MEFV gene mutations and sacroiliitis as a dominant feature of AS. But another question still remains that is there any possible relation between these mutations and other inflammatory arthritis?

There are other studies which carried on patients with rheumatoid arthritis (RA). Most of them assessed the most common mutations of MEFV gene, but, none of them reported an association between MEFV gene mutations and rheumatoid arthritis [11,18-21]. The study which performed in 2005, showed increased mutation rate of exon 2 of MEFV gene (E148Q) in patients with RA, but, the influence to the prognosis was less likely [22,23]. We also performed genetic study on exon 2 and 10 of MEFV gene on thirty four patients with refractory rheumatoid arthritis and healthy control subjects. The results of our study was the same, there was no significant relationship between MEFV gene mutations and patients with refractory rheumatoid arthritis [24,25]. The Table 2 presents the studies conducted on patients with rheumatoid arthritis (RA).


The results of our present study, along with above mentioned published literature, indicate that the prevalence of MEFV gene mutations in patients with ankylosing spondylitis is significant. There is positive relation between common MEFV gene mutations and sacroiliitis. Nevertheless, the influence to the prognosis is less likely. The prevalence of MEFV gene mutations in RA patients is possibly low and not significant. According to the literature review, further studies are needed to investigate the existence of MEFV gene mutations among AS patients and their impact on the disease course in addition to assessment of AS prevalence in patients with FMF.

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2.     Bernot A (1998) Non-founder mutations in the MEFV gene establish this gene as the cause of familial Mediterranean fever (FMF). Hum Mol Genet 7: 1317-1325.

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21.  Koca SS, Etem EO, Isik B, Yuce H, Ozgen M, et al. (2010) Prevalence and significance of MEFV gene mutations in a cohort of patients with rheumatoid arthritis. Joint Bone Spine 77: 32-35.

22.  Rabinovich E, Livneh A, Langevitz P, Brezniak N, Shinar E, et al. (2005) Severe disease in patients with rheumatoid arthritis carrying a mutation in the Mediterranean fever gene. Ann Rheum Dis 64: 1009-1014.

23.  Khabbazi A, Zolrahim F, Estiar MA, Sakhinia E, Kolahi S (2016) Molecular analysis of MEFV gene polymorphisms and mutations in Iranian Azeri patients with rheumatoid arthritis. Iran J Public Health 45: 1383-1385.

24.  Mirzaei A (2018) Assessment of common exon 10 MEFV gene mutations in patients with refractory rheumatoid arthritis. Arch Orthop Rheumatol 1: 1-6.

25.  Mirzaei A, Kolahi S, Ahmadi A, Nakhjavani M, Pashaiasl M (2018) An analysis on pyrin E148Q mutations in patients with refractory rheumatoid arthritis. Rheumatology (Sunnyvale) 8: 2161-1149.