Download PDF
J Pediatr Genet 2022; 11(02): 091-098
DOI: 10.1055/s-0040-1719053
Original Article

Association of Macrophage Migration Inhibitory Factor Gene –173 G/C Polymorphism (rs755622) with Familial Mediterranean Fever in Children

Nursen Cakan 
1   Clinic of Pediatrics, Tokat State Hospital, Tokat, Turkey
,
Resul Yılmaz 
2   Division of Pediatric Critical Care, Department of Pediatrics, Selcuk University School of Medicine, Konya, Turkey
,
Erhan Karaaslan 
3   Department of Pediatrics, Gaziosmanpasa University School of Medicine, Tokat, Turkey
,
Ömer Ateş 
4   Department of Medical Biology and Genetics, Gaziosmanpasa University School of Medicine, Tokat, Turkey
› Author Affiliations Funding This study was supported by Gaziosmanpasa University research fund (project number: 2013/33)
› Further Information
    Permissions and Reprints

Abstract

Objectives The aim of this study was to identify the genotypic analysis and allele frequencies of the –173 G/C polymorphism in the macrophage migration inhibitory factor (MIF) gene in children diagnosed with familial Mediterranean fever (FMF).

Methods The study included 98 children who were diagnosed with FMF according to the Tel Hashomer criteria and one hundred and 57 healthy children as the control group. Genotyping was done for a polymorphism in a promoter region of the MIF gene (G/C at position –173).

Results The relationship of FMF prevalence and –173 G/C genotype of the MIF gene was statistically significant. Individuals with the CC genotype seem to be predisposed to FMF.

Conclusion The C/C polymorphism at position –173 of the MIF gene could be associated with excessive inflammation and immune response and can lead to susceptibility to FMF

Keywords

familial Mediterranean fever - disease severity score - macrophage migration inhibitory factor - gene polymorphism

Ethical Approval

The study was approved by the Gaziosmanpasa University Clinical Research Ethics Committee (ref. no.: 12-GOKAEK-011). All procedures were conducted after written informed consent was obtained from patients or guardians.




Publication History

Received: 27 April 2020

Accepted: 18 September 2020

Article published online:
25 November 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Padeh S. Periodic fever syndromes. Pediatr Clin North Am 2005; 52 (02) 577-609 , vii
    CrossrefPubMedGoogle Scholar
  • 2 Ben-Chetrit E, Touitou I. Familial mediterranean fever in the world. Arthritis Rheum 2009; 61 (10) 1447-1453
    CrossrefPubMedGoogle Scholar
  • 3 Sohar E, Gafni J, Pras M, Heller H. Familial Mediterranean fever. A survey of 470 cases and review of the literature. Am J Med 1967; 43 (02) 227-253
    CrossrefPubMedGoogle Scholar
  • 4 Ben-Chetrit E, Levy M. Familial Mediterranean fever. Lancet 1998; 351 (9103): 659-664
    CrossrefPubMedGoogle Scholar
  • 5 Yilmaz R, Ozer S, Ozyurt H, Erkorkmaz U, Sahin S. Familial Mediterranean fever gene mutations in the inner northern region of Turkey and genotype-phenotype correlation in children. J Paediatr Child Health 2009; 45 (11) 641-645
    CrossrefPubMedGoogle Scholar
  • 6 Pras M. Familial Mediterranean fever: from the clinical syndrome to the cloning of the pyrin gene. Scand J Rheumatol 1998; 27 (02) 92-97
    CrossrefPubMedGoogle Scholar
  • 7 Lue H, Kleemann R, Calandra T, Roger T, Bernhagen J. Macrophage migration inhibitory factor (MIF): mechanisms of action and role in disease. Microbes Infect 2002; 4 (04) 449-460
    CrossrefPubMedGoogle Scholar
  • 8 Flaster H, Bernhagen J, Calandra T, Bucala R. The macrophage migration inhibitory factor-glucocorticoid dyad: regulation of inflammation and immunity. Mol Endocrinol 2007; 21 (06) 1267-1280
    CrossrefPubMedGoogle Scholar
  • 9 Kang I, Bucala R. The immunobiology of MIF: function, genetics and prospects for precision medicine. Nat Rev Rheumatol 2019; 15 (07) 427-437
    CrossrefPubMedGoogle Scholar
  • 10 Harris J, VanPatten S, Deen NS, Al-Abed Y, Morand EF. Rediscovering MIF: new tricks for an old cytokine. Trends Immunol 2019; 40 (05) 447-462
    CrossrefPubMedGoogle Scholar
  • 11 Leech M, Lacey D, Xue JR. et al. Regulation of p53 by macrophage migration inhibitory factor in inflammatory arthritis. Arthritis Rheum 2003; 48 (07) 1881-1889
    CrossrefPubMedGoogle Scholar
  • 12 Morand EF, Leech M, Weedon H, Metz C, Bucala R, Smith MD. Macrophage migration inhibitory factor in rheumatoid arthritis: clinical correlations. Rheumatology (Oxford) 2002; 41 (05) 558-562
    CrossrefPubMedGoogle Scholar
  • 13 Illescas O, Gomez-Verjan JC, García-Velázquez L, Govezensky T, Rodriguez-Sosa M. Macrophage migration inhibitory factor-173 G/C polymorphism: a global meta-analysis across the disease spectrum. Front Genet 2018; 9: 55
    CrossrefPubMedGoogle Scholar
  • 14 Donn RP, Plant D, Jury F. et al. Macrophage migration inhibitory factor gene polymorphism is associated with psoriasis. J Invest Dermatol 2004; 123 (03) 484-487
    CrossrefPubMedGoogle Scholar
  • 15 Nohara H, Okayama N, Inoue N. et al. Association of the -173 G/C polymorphism of the macrophage migration inhibitory factor gene with ulcerative colitis. J Gastroenterol 2004; 39 (03) 242-246
    CrossrefPubMedGoogle Scholar
  • 16 Wang F-F, Huang X-F, Shen N. et al. A genetic role for macrophage migration inhibitory factor (MIF) in adult-onset Still's disease. Arthritis Res Ther 2013; 15 (03) R65
    CrossrefPubMedGoogle Scholar
  • 17 Santoscoy-Ascencio G, Baños-Hernández CJ, Navarro-Zarza JE. et al. Macrophage migration inhibitory factor promoter polymorphisms are associated with disease activity in rheumatoid arthritis patients from Southern Mexico. Mol Genet Genomic Med 2020; 8 (01) e1037
    CrossrefPubMedGoogle Scholar
  • 18 Bilsborrow JB, Doherty E, Tilstam PV, Bucala R. Macrophage migration inhibitory factor (MIF) as a therapeutic target for rheumatoid arthritis and systemic lupus erythematosus. Expert Opin Ther Targets 2019; 23 (09) 733-744
    CrossrefPubMedGoogle Scholar
  • 19 Zheng X, Wang D, Hou S. et al. Association of macrophage migration inhibitory factor gene polymorphisms with Behçet's disease in a Han Chinese population. Ophthalmology 2012; 119 (12) 2514-2518
    CrossrefPubMedGoogle Scholar
  • 20 Pras M, Kastner DL. Familial Mediterranean fever. In: Klippel JH, Dieppe PA. eds. Rheumatology. 2nd ed. London: Mosby; 2000: 1-4
    Google Scholar
  • 21 Gürel Ç, İnanır A, Nursal AF, Tekcan A, Rüstemoğlu A, Yigit S. Evaluation of MIF -173 G/C polymorphism in Turkish patients with ankylosing spondylitis. Balkan Med J 2016; 33 (06) 614-619
    CrossrefPubMedGoogle Scholar
  • 22 Makhija R, Kingsnorth A, Demaine A. Gene polymorphisms of the macrophage migration inhibitory factor and acute pancreatitis. JOP 2007; 8 (03) 289-295
    PubMedGoogle Scholar
  • 23 Stojanov S, Kastner DL. Familial autoinflammatory diseases: genetics, pathogenesis and treatment. Curr Opin Rheumatol 2005; 17 (05) 586-599
    CrossrefPubMedGoogle Scholar
  • 24 Touitou I, Lesage S, McDermott M. et al. Infevers: an evolving mutation database for auto-inflammatory syndromes. Hum Mutat 2004; 24 (03) 194-198
    CrossrefPubMedGoogle Scholar
  • 25 Dundar M, Kiraz A, Balta B. et al. The role of TNF-α and PAI-1 gene polymorphisms in familial Mediterranean fever. Mod Rheumatol 2013; 23 (01) 140-145
    CrossrefPubMedGoogle Scholar
  • 26 Popa C, van Lieshout AW, Roelofs MF. et al. MIF production by dendritic cells is differentially regulated by Toll-like receptors and increased during rheumatoid arthritis. Cytokine 2006; 36 (1-2): 51-56
    CrossrefPubMedGoogle Scholar
  • 27 Onodera S, Nishihira J, Koyama Y. et al. Macrophage migration inhibitory factor up-regulates the expression of interleukin-8 messenger RNA in synovial fibroblasts of rheumatoid arthritis patients: common transcriptional regulatory mechanism between interleukin-8 and interleukin-1β. Arthritis Rheum 2004; 50 (05) 1437-1447
    CrossrefPubMedGoogle Scholar
  • 28 Sampey AV, Hall PH, Mitchell RA, Metz CN, Morand EF. Regulation of synoviocyte phospholipase A2 and cyclooxygenase 2 by macrophage migration inhibitory factor. Arthritis Rheum 2001; 44 (06) 1273-1280
    CrossrefPubMedGoogle Scholar
  • 29 Denkinger CM, Metz C, Fingerle-Rowson G, Denkinger MD, Forsthuber T. Macrophage migration inhibitory factor and its role in autoimmune diseases. Arch Immunol Ther Exp (Warsz) 2004; 52 (06) 389-400
    PubMedGoogle Scholar
  • 30 Kasama T, Ohtsuka K, Sato M, Takahashi R, Wakabayashi K, Kobayashi K. Macrophage migration inhibitory factor: a multifunctional cytokine in rheumatic diseases. Arthritis (Egypt) 2010; 2010: 106202
    PubMedGoogle Scholar
  • 31 Donn RP, Shelley E, Ollier WE, Thomson W. British Paediatric Rheumatology Study Group. A novel 5′-flanking region polymorphism of macrophage migration inhibitory factor is associated with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 2001; 44 (08) 1782-1785
    CrossrefPubMedGoogle Scholar
  • 32 Yildiz G, Kayatas M, Uygun Y, Timuçin M, Candan F. Coexistence of systemic lupus erythematosus and familial Mediterranean fever. Intern Med 2010; 49 (08) 767-769
    CrossrefPubMedGoogle Scholar
  • 33 Aksu K, Keser G. Coexistence of vasculitides with familial Mediterranean fever. Rheumatol Int 2011; 31 (10) 1263-1274
    CrossrefPubMedGoogle Scholar
  • 34 Ergul AB, Dursun I, Torun YA. Hashimoto's thyroiditis in a child with familial mediterranean fever: a case report. Iran J Pediatr 2013; 23 (04) 489-490
    PubMedGoogle Scholar
  • 35 Erten S, Taskaldiran I, Yakut ZI. Are systemic lupus erythematosus patients carrying MEFV gene less prone to renal involvement? Report of three cases and review of the literature. Ren Fail 2013; 35 (07) 1013-1016
    CrossrefPubMedGoogle Scholar
  • 36 Renner P, Roger T, Calandra T. Macrophage migration inhibitory factor: gene polymorphisms and susceptibility to inflammatory diseases. Clin Infect Dis 2005; 41 (Suppl. 07) S513-S519
    CrossrefPubMedGoogle Scholar
  • 37 Donn R, Alourfi Z, Zeggini E. British Paediatric Rheumatology Study Group. et al. A functional promoter haplotype of macrophage migration inhibitory factor is linked and associated with juvenile idiopathic arthritis. Arthritis Rheum 2004; 50 (05) 1604-1610
    CrossrefPubMedGoogle Scholar
  • 38 Pakozdi A, Amin MA, Haas CS. et al. Macrophage migration inhibitory factor: a mediator of matrix metalloproteinase-2 production in rheumatoid arthritis. Arthritis Res Ther 2006; 8 (04) R132
    CrossrefPubMedGoogle Scholar
  • 39 Martínez A, Orozco G, Varadé J. et al. Macrophage migration inhibitory factor gene: influence on rheumatoid arthritis susceptibility. Hum Immunol 2007; 68 (09) 744-747
    CrossrefPubMedGoogle Scholar
  • 40 Liu R, Xu N, Wang X. et al. Influence of MIF, CD40, and CD226 polymorphisms on risk of rheumatoid arthritis. Mol Biol Rep 2012; 39 (06) 6915-6922
    CrossrefPubMedGoogle Scholar
  • 41 De Benedetti F, Meazza C, Vivarelli M. British Paediatric Rheumatology Study Group. et al. Functional and prognostic relevance of the -173 polymorphism of the macrophage migration inhibitory factor gene in systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 2003; 48 (05) 1398-1407
    CrossrefPubMedGoogle Scholar
  • 42 Sánchez E, Gómez LM, Lopez-Nevot MA. et al. Evidence of association of macrophage migration inhibitory factor gene polymorphisms with systemic lupus erythematosus. Genes Immun 2006; 7 (05) 433-436
    CrossrefPubMedGoogle Scholar
  • 43 Rigante D, Flex A, Federico G. et al. Serum macrophage migration inhibitory factor (MIF) in the intercritical phase of hereditary periodic fevers and its relationship with the MIF-173G/C polymorphism. Scand J Rheumatol 2007; 36 (04) 307-310
    CrossrefPubMedGoogle Scholar
  • 44 Çakmak E, Ece A, Kelekçi S, Yolbaş İ, Güneş A, Şen V. Comparison of acute phase response during attack and attack-free period in children with familial Mediterranean Fever. J Clin Exp Invest 2013; 4: 231-18
    PubMedGoogle Scholar
  • 45 Özer S, Yılmaz R, Sönmezgöz E. et al. Simple markers for subclinical inflammation in patients with familial Mediterranean fever. Med Sci Monit 2015; 21: 298-303
    CrossrefPubMedGoogle Scholar
  • 46 Llamas-Covarrubias MA, Valle Y, Navarro-Hernández RE. et al. Serum levels of macrophage migration inhibitory factor are associated with rheumatoid arthritis course. Rheumatol Int 2012; 32 (08) 2307-2311
    CrossrefPubMedGoogle Scholar
  • 47 Dambacher J, Staudinger T, Seiderer J. et al. Macrophage migration inhibitory factor (MIF) -173G/C promoter polymorphism influences upper gastrointestinal tract involvement and disease activity in patients with Crohn's disease. Inflamm Bowel Dis 2007; 13 (01) 71-82
    CrossrefPubMedGoogle Scholar
  • 48 Assis DN, Takahashi H, Leng L, Zeniya M, Boyer JL, Bucala R. A macrophage migration inhibitory factor polymorphism is associated with autoimmune hepatitis severity in US and Japanese patients. Dig Dis Sci 2016; 61 (12) 3506-3512
    CrossrefPubMedGoogle Scholar
  • 49 Barton A, Lamb R, Symmons D. et al. Macrophage migration inhibitory factor (MIF) gene polymorphism is associated with susceptibility to but not severity of inflammatory polyarthritis. Genes Immun 2003; 4 (07) 487-491
    CrossrefPubMedGoogle Scholar
  • 50 Radstake TR, Sweep FC, Welsing P. et al. Correlation of rheumatoid arthritis severity with the genetic functional variants and circulating levels of macrophage migration inhibitory factor. Arthritis Rheum 2005; 52 (10) 3020-3029
    CrossrefPubMedGoogle Scholar
  • 51 Baugh JA, Chitnis S, Donnelly SC. et al. A functional promoter polymorphism in the macrophage migration inhibitory factor (MIF) gene associated with disease severity in rheumatoid arthritis. Genes Immun 2002; 3 (03) 170-176
    CrossrefPubMedGoogle Scholar
  • 52 Yao J, Leng L, Sauler M. et al. Transcription factor ICBP90 regulates the MIF promoter and immune susceptibility locus. J Clin Invest 2016; 126 (02) 732-744
    CrossrefPubMedGoogle Scholar
  • 53 De la Cruz-Mosso U, Bucala R, Palafox-Sánchez CA. et al. Macrophage migration inhibitory factor: association of -794 CATT5-8 and -173 G>C polymorphisms with TNF-α in systemic lupus erythematosus. Hum Immunol 2014; 75 (05) 433-439
    CrossrefPubMedGoogle Scholar
  • 54 Morales-Zambrano R, Bautista-Herrera LA, De la Cruz-Mosso U. et al. Macrophage migration inhibitory factor (MIF) promoter polymorphisms (-794 CATT5-8 and -173 G>C): association with MIF and TNFα in psoriatic arthritis. Int J Clin Exp Med 2014; 7 (09) 2605-2614
    PubMedGoogle Scholar
  • 55 Sreih AG, Ezzedine R, Leng L. et al. Role of macrophage migration inhibitory factor in granulomatosis with polyangiitis. Arthritis Rheumatol 2018; 70 (12) 2077-2086
    CrossrefPubMedGoogle Scholar