Common Mediterranean Fever (MEFV) Gene Mutations Associated with Ankylosing Spondylitis in Turkish Population

Ankylosing spondylitis (AS) is a common inflammatory rheumatic disease. Mediterranean fever (MEFV) gene, which has already been identified as being responsible for familial Mediterranean fever (FMF), is also a suspicious gene for AS because of the clinical association of these two diseases. The aim of this study was to explore the frequency and clinical significance ofMEFVgene mutations (M694V, M680I, V726A, E148Q and P369S) in a cohort of Turkish patients with AS. Genomic DNAs of 103 AS patients and 120 controls were isolated and genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods. There was a statistically significant difference of theMEFVgene mutation carrier rates between AS patients and healthy controls (p= 0.004, OR: 2.5, 95% CI: 1.32–4.76). This association was also observed in allele frequencies (p= 0.005, OR: 2.3, 95% CI: 1.27–4.2). A relatively higher frequency was observed for M694V mutation in AS patients than controls (10.7% versus 4.2% ,p= 0.060). There were no significant differences between MEFV mutation carriers and non-carriers with respect to the clinical and demographic characteristics. The results of this study suggest thatMEFVgene mutations are positively associated with a predisposition to develop AS.

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Frequency and Disease Severity of Familial Mediterranean Fever (FMF) Related MEFV Gene Mutations Among Ankylosing Spondylitis Patients

Turkiye Klinikleri Journal of Medical Sciences ◽

10.5336/medsci.2013-34490 ◽

2014 ◽

Vol 34 (2) ◽

pp. 223-230 ◽

Cited By ~ 2

Author(s):

Aslı TUFAN ◽

Sibel Zehra AYDIN ◽

Fatih EREN ◽

Pamir ATAGÜNDÜZ

Keyword(s):

Ankylosing Spondylitis ◽

Familial Mediterranean Fever ◽

Disease Severity ◽

Mefv Gene ◽

Gene Mutations ◽

Mediterranean Fever

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Comparison of Clinical and Demographic Features of FMF with Sacroiliitis Patients with FMF and Axial Spondyloarthritis Patients

Aktuelle Rheumatologie ◽

10.1055/a-1252-2190 ◽

2020 ◽

Author(s):

Esra Dilşat Bayrak ◽

Sukran Erten ◽

Orhan Kucuksahin ◽

Osman Ersoy

Keyword(s):

Inflammatory Markers ◽

Mefv Gene ◽

Gene Mutations ◽

Recurrent Fever ◽

Hla B27 ◽

M694v Mutation ◽

Genetic Features ◽

Mediterranean Fever ◽

Common Manifestation ◽

Musculoskeletal Involvement

Abstract Objectives Familial Mediterranean fever (FMF) is the most common autoinflammatory disease, characterised by recurrent fever and serositis attacks lasting 1–3 days. Musculoskeletal involvement is the second most common manifestation in FMF patients. Sacroiliitis is another musculoskeletal involvement; as there is no spinal involvement, this is called FMF with sacroiliitis. This study was designed to investigate the clinical, demographic and genetic features of FMF in sacroiliitis patients and to compare them with axial SpA and FMF patients. Materials and Methods Forty-two FMF with sacroiliitis patients, 100 axial SpA patients and 100 FMF patients were recruited, and their demographic characteristics were recorded. Evidence of sacroiliitis was confirmed by sacroiliac joint MRI, and patients were examined for arthritis and enthesitis. MEFV gene mutations, HLA B27 positivity and ESR and CRP results were compared. Results In the FMF with sacroiliitis group, the M694V mutation was detected in 59.5% of patients. FMF with sacroiliitis patients were largely (83.3%) negative for HLA B27. The frequency of enthesitis was similar between FMF with sacroiliitis and axial SpA, and the frequency of arthritis was higher in axial SpA patients. Inflammatory markers (ESR and CRP) were statistically higher in FMF with sacroiliitis patients compared with axial SpA and FMF patients. Conclusion When all three groups were compared, the M694V mutation was more common, HLA B27 was largely negative and inflammatory markers were higher in the FMF with sacroiliitis group. FMF should be included in the differential diagnosis of sacroiliitis for managing treatment correctly and preventing complications.

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AB1071 COEXISTENCE OF FAMILIAL MEDITERRANEAN FEVER WITH SPONDYLOARTHRITIS: CLINICAL CHARACTERISTIC AND TREATMENT OUTCOMES

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.4209 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1824.1-1825

Author(s):

T. Yüce İnel ◽

İ. Sari ◽

M. Birlik ◽

G. Can ◽

F. Onen

Keyword(s):

Familial Mediterranean Fever ◽

Treatment Outcomes ◽

Clinical Characteristics ◽

Mefv Gene ◽

Laboratory Data ◽

Gene Mutations ◽

Symptom Duration ◽

Hla B27 ◽

M694v Mutation ◽

Mediterranean Fever

Background:Studies indicate that there is an association with spondyloarthritis (SpA) and familial mediterranean fever (FMF) based on the following: 1) increased incidence of sacroiliitis in FMF, 2) MEFV gene mutations are significantly increased in ankylosing spondylitis (AS) and 3) both SpA and FMF show some common clinical manifestations such as the pattern of arthritis. However, characteristics of SpA associated with FMF such as clinical characteristics and treatment outcomes have been poorly documented and additional data is required on this topic.Objectives:To study the clinical and treatment characteristics of patients associated with FMF and SpA.Methods:Twenty-eight patients with FMF and SpA who were registered in our database were included in the study. Demographic, clinical, and laboratory data were collected. HLA-B27, MEFV gene mutations were recorded. Pelvic radiographs and sacroiliac joint magnetic resonance imaging (MRI) (if present) were scored based on the modified New York criteria (mNYc) and ASAS MRI definitions respectively. Treatment data were also recorded.Results:There were 28 FMF-SpA patients in the study (mean age 45.1±16.4 years, 57.2% male). The mean age of onset of FMF and SpA were 31.9±17.9 and 35.5±16.2 years respectively. SpA patients were predominantly axial (n=21, 75%), and only 7 (25%) were mainly peripheral type. Fifteen (53.5%) patients were satisfying mNYc for AS. Four (14%) patients were fulfilling ASAS non radiographic axial SpA definition. Bone marrow edema was detected in (36%) of the patients who underwent MRI (n=14). Two (7.1%) patients had SpA symptoms but did not classify into any of the ASAS arms. Arthritis observed in 19 (67.8%) patients with mostly in oligoarthritis type (79%). Ankle and knees were the most affected joints. Total hip replacement was present in 7% of the patients. Amyloidosis confirmed by biopsy was detected in 4 (14%) patients. Enthesitis (11%), uveitis (11%), Chron’s disease (7%), dactylitis (3%), and psoriasis (3%) was also noted. Nearly %30 patients required non IL-1 biologic therapy (BTx) to control SpA symptoms (axial 70%, peripheral 30%). 40% of the patients needed to switch non IL-1 BTx to another biologic agent because of lack of efficacy on SpA symptoms (25%) or due to the adverse event (25%) and active FMF not responding to non IL-1 biological agent (50%).Conclusion:We showed the following: 1) more female predominance in FMF-SpA patients compared to classic SpA, 2) FMF-SpA patients had lower frequency of HLA B27, 3) up to %30 of the patients required non-IL-1 BTx to control SpA symptoms and 4) in patients on non IL-1 BTx FMF symptoms responded in 80%.Table 1.The clinical characteristics of FMF-SPA patientsAge*45.1±16.4Male, n (%)16 (57.2)SpA symptom duration,years*9.5±7.0FMF symptom duration,years*12.6±9.6HLA-B27 positivity, n (%)5 (29.4)Mainly axial involvement, n (%)21 (75)Mainly peripheral involvement, n (%)7(25)mNY positivity, n (%)15 (53.5)MEFV (M694V) mutation18MEFV (non M694V) mutation19Amyloidosis, n (%)4 (14.2)Non IL-1 biological treatment for SpA symptoms, n (%)10 (35.7)*(mean ±S.D)Disclosure of Interests:None declared

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MEFV gene mutations in Iranian patients with familial mediterranean fever (FMF)

The American Journal of Gastroenterology ◽

10.1016/s0002-9270(03)00980-8 ◽

2003 ◽

Vol 98 (9) ◽

pp. S72-S73 ◽

Cited By ~ 1

Author(s):

M ZALI

Keyword(s):

Familial Mediterranean Fever ◽

Mefv Gene ◽

Gene Mutations ◽

Mediterranean Fever ◽

Iranian Patients

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The Frequency of Familial Mediterranean Fever Gene Mutations and the Correlations between Phenotype and Genotype in Turkish Children

Asian Journal of Pediatric Research ◽

10.9734/ajpr/2020/v4i230145 ◽

2020 ◽

pp. 20-26

Author(s):

Hakan Erdogan ◽

Ayse Cavidan Sonkur ◽

Orhan Görükmez ◽

Ayse Erdogan ◽

Dilek Damla Saymazlar ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Mutation Screening ◽

Mefv Gene ◽

Gene Mutations ◽

Retrospective Case ◽

Turkish Children ◽

Pathogenic Variants ◽

Frequent Mutations ◽

Training And Research ◽

Mediterranean Fever

Aim: Familial Mediterranian Fever is an autosomal recessive disease characterized by recurrent inflammatory attacks of serosal membranes. The aim of the current study was to determine the frequency of the Mediterranean fever (MEFV) gene pathogenic variants in 158 children (78 male, 80 female) diagnosed with Familial Mediterranean Fever (FMF) and to compare the phenotype-genotype correlation. Methods: In our retrospective case-control study, 158 FMF patients (78 males, 80 females) who were diagnosed with MEFV gene mutation in Bursa Yuksek Ihtisas Training and Research Hospital, Department of Pediatrics between January 2018 and June 2019 were included in the study. Mutation screening of the MEFV gene was performed for 12 mutations and the 8 most common mutations were taken into the study. Results: Abdominal pain (77.8%), fever (74%) and arthralgia (46.2%) were the most prevalent clinical features in our patients. The most frequent mutations were M694V, E148Q, V726A, M680I and P369S. In cases with M694 mutation, it was noted that the incidence of arthritis was 2.5 times, appendectomy frequency 3.1 times higher, and early diagnosis probability 3.2 times higher. The frequency of chest pain was 2.9 times higher in the M680I mutation, and the frequency of arthralgia was 2.2 times higher in the P369S mutation. Conclusion: Patient’s mutations in FMF patients are important for clinical expectations, and some mutations such as P369S are not as innocent as expected. However, reevaluation of phenotypes of mutations that are rare with more patients will be significant.

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R202Q/M694V as novel MEFV gene mutations in chronic periodontitis and familial Mediterranean fever

Journal of Periodontal Research ◽

10.1111/jre.12467 ◽

2017 ◽

Vol 52 (6) ◽

pp. 994-1003 ◽

Cited By ~ 3

Author(s):

Ö. Fentoğlu ◽

G. Dinç ◽

Ö. Bağcı ◽

A. Doğru ◽

İ. İlhan ◽

...

Keyword(s):

Familial Mediterranean Fever ◽

Chronic Periodontitis ◽

Mefv Gene ◽

Gene Mutations ◽

Mediterranean Fever

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Association of HLA-B27, MEFV gene mutations, ERAP1, IL12B and IL23R gene polymorphisms with ankylosing spondylitis.

Turkish Journal of Biochemistry ◽

10.5505/tjb.2014.44265 ◽

2014 ◽

Author(s):

Engin Yilmaz

Keyword(s):

Ankylosing Spondylitis ◽

Gene Polymorphisms ◽

Mefv Gene ◽

Gene Mutations ◽

Hla B27

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MTHFRGene C677T Mutation andACEGene I/D Polymorphism in Turkish Patients with Osteoarthritis

Disease Markers ◽

10.1155/2013/658654 ◽

2013 ◽

Vol 34 (1) ◽

pp. 17-22 ◽

Cited By ~ 9

Author(s):

Ahmet Inanir ◽

Serbulent Yigit ◽

Sengul Tural ◽

Osman Cecen ◽

Eren Yildirim

Keyword(s):

Polymerase Chain Reaction ◽

Methylenetetrahydrofolate Reductase ◽

Chain Reaction ◽

Gene Insertion ◽

Significant Difference ◽

Joint Disorder ◽

Allele Specific ◽

C677t Mutation ◽

Polymerase Chain ◽

Turkish Patients

Osteoarthritis is a degenerative joint disorder resulting in destruction of articular cartilage, osteophyte formation, and subchondral bone sclerosis. In recent years, numerous genetic factors have been identified and implicated in osteoarthritis. The aim of the current study was to examine the influence of methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation and angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) variations on the risk of osteoarthritis.Genomic DNA is obtained from 421 persons (221 patients with osteoarthritis and 200 healthy controls).ACEgene I/D polymorphism genotypes were determined using polymerase chain reaction using I and D allele-specific primers. TheMTHFRC677T mutation was analyzed by polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP) methods. We found significant difference between the groups with respect to bothACEandMTHFRgenotype distributions (p< 0.001,p< 0.001 respectively). Our study suggests thatACEgene DD genotype andMTHFRgene CC genotype could be used as genetic markers in osteoarthritis in Turkish study populations.

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