Abstract
Background
Familial Mediterranean fever (FMF) is an autosomal recessive genetic disease. Amyloidosis is the most important complication of FMF that determines the prognosis of the disease.
Aims
In our study, we have investigated the relationship between the genetic mutations with the disease severity and the frequency of development of amyloidosis inpatients with FMF.
Methods
A total of 148 patients with FMF were included this study. The relationship between disease activity score, clinical findings, response to treatment, and presence of amyloid and genetic mutations were evaluated.
Results
One hundred forty-eight patients (80 women (54%), 68 men (46%)) were enrolled over 18 years of age. The mean age of the patients was 30.98 ± 11.18 (18–67) years. In our study, the most frequently seen mutations are M694V, M680I, R202Q, and E148Q, respectively. The most common genotype is M694V/M694V mutation and this mutation has been found in 37 patients (25%). In 25 patients, M694V heterozygous have been found (16.8%). The third frequent mutationis M694V/M680I/R202Q has been found in13 patients (8.7%). In 23 patients, amyloidosis has been developed. Ten patients with amyloidosis have M694V homozygous mutations (27%) and 5 patients with amyloidosis M694V heterozygous (20%) mutations. The both of the two patients who carry the homozygous E148Q mutations have developed amyloidosis.
Conclusions
In our study, the distribution of the frequency of mutations is consistent with other similar studies performed in Turkey. We found that patients with M694V mutation had a significantly higher rate of exacerbation, higher drug doses for treatment, and a close relationship with amyloidosis, as compared to patients with other mutations.
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References
Ben-Chetrit E, Touitou I (2009) Familial Mediterranean Fever in the world. Arthritis Rheum 61:1447–1453. https://doi.org/10.1002/art.24458
Ben-Chetrit E, Yazici H (2019) Familial Mediterranean fever: different faces around the world. Clin Exp Rheumatol 37:Suppl 121–18–22
Yilmaz E, Ozen S, Balci B et al (2001) Mutation frequency of familial Mediterranean fever and evidence for a high carrier rate in the Turkish population. Eur J Hum Genet 9:553–555. https://doi.org/10.1038/sj.ejhg.5200674
Pras E, Aksentijevich I, Gruberg L et al (1992) Mapping of a gene causing familial Mediterranean fever to the short arm of chromosome 16. N Engl J Med 326:1509–1513. https://doi.org/10.1056/NEJM199206043262301
Levy EN, Shen Y, Kupelian A et al (1996) Linkage disequilibrium mapping places the gene causing familial Mediterranean fever close to D16S246. Am J Hum Genet 58:523–534
Touitou I (2001) The spectrum of familial Mediterranean fever (FMF) mutations. Eur J Hum Genet 9:473–483. https://doi.org/10.1038/sj.ejhg.5200658
Pras E, Livneh A, Balow JE Jr et al (1998) Clinical differences between North African and Iraqi Jews with familial Mediterranean fever. Am J Med Genet 75:216–219. https://doi.org/10.1002/(sici)1096-8628(19980113)75:2%3c216::aid-ajmg20%3e3.0.co;2-r
Erguven M, Ucel R, Cebeci AN, Pelit M (2006) Demographic, clinical and genetic characteristics of familial Mediterranean fever and response to treatment: 120 vakalık tek merkez deneyimi. J Child Health Dis 49:283–290
Papa R, Lachmann HJ (2018) Secondary amyloidosis. Rheum Dis Clin North Am 44(585):603. https://doi.org/10.1016/j.rdc.2018.06.004
Mattit H, Joma M, Al-Cheikh S et al (2006) Familial Mediterranean fever in the Syrian population: gene mutation frequencies, carrierrates and phenotype-genotype correlation. Eur J Med Genet 49:481–486. https://doi.org/10.1016/j.ejmg.2006.03.002
Nursal AF, Tekcan A, Kaya SU, Turkmen E, Yigit S (2016) Mutational spectrum of the MEFV gene in AA amyloidosis associated with familial mediterranean fever. Iran J Kidney Dis 10:107–112
Booty MG, Chae JJ, Masters SL et al (2009) Familial Mediterranean fever with a single MEFV mutation: where is the second hit? Arthritis Rheum 60:1851–1861. https://doi.org/10.1002/art.24569
Akar N, Mısıroğlu M, Yalçınkaya F et al (2000) MEFV mutations in Turkish patients suffering from familial Mediterranean fever. Hum Mutat 15:118–119. https://doi.org/10.1002/(SICI)1098-1004(200001)15:1%3c118::AID-HUMU29%3e3.0.CO;2-5
Gershoni-Baruch R, Brik R, Shinawi M, Livneh A (2002) The differential contribution of MEFV mutant alleles to the clinical profile of familial Mediterranean fever. Eur J Hum Genet 10:145–149. https://doi.org/10.1038/sj.ejhg.5200776
Livneh A, Langevitz P, Shinar Y et al (1999) MEFV mutation analysis in patients suffering from amyloidosis of familial Mediterranean fever Amyloid: Int. J Exp Clin Invest 6:1–6. https://doi.org/10.3109/13506129908993281
Kasifoglu T, Bilge SY, Sarı İ et al (2014) Amyloidosis and its related factors in Turkish patientswith familial Mediterranean fever: a multicentre study. Rheumatology 53:741–745. https://doi.org/10.1093/rheumatology/ket400
Dewalle M, Domingo C, Rozenbaum M et al (1998) Phenotype genotype correlation in Jewish patients suffering from familial Mediterranean fever: evidence for an association between Met694Val and amiloidosis. Eur J Hum Gene 6:95–97. https://doi.org/10.1038/sj.ejhg.5200170
Yalçmkaya F, Çakar N, Mısırlıoğlu M et al (2000) Phenotype genotype correlation in a large group of Turkish patients with familial Mediterranean fever: evidence for mutation independent amyloidosis. Rheumatology 39:67–72. https://doi.org/10.1093/rheumatology/39.1.67
Booth DR, Gillmore JD, Booth SE et al (1998) Pyrin/marenostrin mutations in familial Mediterranean fever. Q J Med 91:630–636. https://doi.org/10.1093/qjmed/91.9.603
Chen X, Fischel-Ghodsian N, Cercek A et al (1998) Assessment of pyrin gene mutations in Turks with familial Mediterranean fever (FMF). Hum Mutat 11:456–460. https://doi.org/10.1002/(SICI)1098-1004(1998)11:6<456::AID-HUMU6>3.0.CO;2-G
Yalçınkaya F, Akar N, Mısırlıoğlu M (1998) Familial Mediterranean fever- amyloidosis and the Val726Ala mutation. N Eng J Med Genet 338:993–994. https://doi.org/10.1056/NEJM199804023381414
Tunca M, Akar S, Onen F et al (2005) Familial Mediterranean fever (FMF) in Turkey: results of a nationwide multicenter study. Medicine (Baltimore) 84:1–11. https://doi.org/10.1097/01.md.0000152370.84628.0c
Touitou I, Sarkisian T, Medlej-Hashim M et al (2007) Country as the primary risk factor for renal amyloidosis in familial Mediterranean fever. Arthritis Rheum 56:1706–1712. https://doi.org/10.1002/art.2250717
Majeed HA, Rawashdeh M, el-Shanti H et al (1999) Familial Mediterranean fever in children: the expanded clinical profile. QJM 92:309–318. https://doi.org/10.1093/qjmed/92.6.309
Gedalia A, Adar A, Gorodischer R (1992) Familial Mediterranean fever in children J Rheumatol Suppl 35:1–9
Bilge SY, Sari I, Solmaz D et al (2019) The distribution of MEFV mutations in Turkish FMF patients: multicenter study representing results of Anatolia. Turk J Med Sci 18:472–477. https://doi.org/10.3906/sag-1809-100
Ozcan AG, Sayin DB, Misirlioğlu ED et al (2009) The spectrum of FMF mutations and genotypes in the referrals to molecular genetic laboratory at Kirikkale University in Turkey. Mol Biol Rep 36:757–760. https://doi.org/10.1007/s11033-008-9240-9245
Acknowledgements
We would like to thank Prof. Dr. Hasan Önder, faculty member of 19 Mayıs University Faculty of Agriculture, Department of Zootechnics, who contributed to the statistical evaluation of the study.
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Ethics committee approval, numbered B.30.2.ODM.0.20.08/225–296 and dated 17.05.2016, was obtained from the Ethics Committee of Ondokuz Mayıs University Faculty of Medicine. All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
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Bas, B., Sayarlioglu, H., Yarar, Z. et al. Investigation of the relationship between disease severity and development of amyloidosis and genetic mutation in FMF disease. Ir J Med Sci 192, 1497–1503 (2023). https://doi.org/10.1007/s11845-022-03108-5
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DOI: https://doi.org/10.1007/s11845-022-03108-5