Association of Macrophage Migration Inhibitory Factor Gene Promoter Polymorphisms with Multiple Sclerosis in Turkish Patients

Abstract

Elevated levels of macrophage migration inhibitory factor (MIF) have been observed in the cerebrospinal fluid of patients with multiple sclerosis. This study was designed to determine if MIF gene polymorphisms are associated with multiple sclerosis and disease severity. In total, 120 relapsing-remitting patients with multiple sclerosis and 120 control subjects were enrolled in the study. There was a statistically significant increase in the MIF −173 CC genotype in patients with multiple sclerosis compared with the control subjects. The MIF −794 6/7 genotype had a significantly lower progression index compared with MIF −794 6/6. Patients with the MIF −173 CC genotype had a significantly lower age of disease onset compared with those with the MIF −173 CG and MIF −173 GG genotypes. Additionally, patients with the MIF −794 5/6 genotype had a significantly later age of disease onset. This study indicates that the MIF −173 CC genotype may cause susceptibility to multiple sclerosis in the white Turkish population and a younger age of disease onset is associated with this polymorphism.

Keywords

Multiple sclerosis Migration inhibitory factor (MIF)Promoter polymorphisms Onset age Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)

References

Noseworthy

Lucchinetti

Rodrigez

: Multiple sclerosis. N Engl J Med 2000; 343: 938–952.

Ramagopalan

Dyment

Ebers

: Genetic epidemiology: The use of old and new tools for multiple sclerosis. Trends Neurosci 2008; 31: 645–652.

Olerup

Hillert

: HLA class II-associated genetic susceptibility in multiple sclerosis: A critical evaluation. Tissue Antigens 1991; 38: 1–15.

Dyment

Ebers

Sadovnick

: Genetics of multiple sclerosis. Lancet Neurol 2004; 3: 104–110.

Hafler

Compston

Sawcer S, et al for the International Multiple Sclerosis Genetics Consortium: Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med 2007; 357: 851–862.

Lundmark

Duvefelt

Iacobaeus

: Variation in interleukin 7 receptor α chain (IL7R) influences risk of multiple sclerosis. Nat Genet 2007; 39: 1108–1113.

Calandra

Roger

: Macrophage migration inhibitory factor: A regulator of innate immunity. Nat Rev Immunol 2003; 3: 791–800.

Bacher

Metz

Calandra

: An essential regulatory role for macrophage migration inhibitory factor in T-cell activation. Proc Natl Acad Sci USA 1996; 93: 7849–7854.

Niino

Ogata

Kikuchi

: Macrophage migration inhibitory factor in the cerebrospinal fluid of patients with conventional and optic-spinal forms of multiple sclerosis and neuro-Behçet's disease. J Neurol Sci 2000; 179 (suppl 1–2): 127–131.

10.

Morand

Bucala

Leech

: Macrophage migration inhibitory factor: An emerging therapeutic target in rheumatoid arthritis. Arthritis Rheum 2003; 48: 291–299.

11.

Lan

Yang

: De novo renal expression of macrophage migration inhibitory factor during the development of rat crescentic glomerulonephritis. Am J Pathol 1996; 149: 1119–1127.

12.

de Jong

Abadia-Molina

Satoskar

: Development of chronic colitis is dependent on the cytokine MIF. Nat Immunol 2001; 2: 1061–1066.

13.

McDonald

Compston

Edan

: Recommended diagnostic criteria for multiple sclerosis: Guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Ann Neurol 2001; 50: 121–127.

14.

The Kurtzke Expanded Disability Status Scale (EDSS). All About Multiple Sclerosis web site. The Multiple Sclerosis Information Trust (available at: http://www.mult-sclerosis.org/expandeddisabilitystatusscale.html).

15.

Miller

Dykes

Polesky

: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215.

16.

Ren

: Association of MIF promoter polymorphisms with childhood asthma in a northeastern Chinese population. Tissue Antigens 2009; 73: 302–306.

17.

Pehlivan

Koyuncuoglu

Pehlivan

: Premalignant lesions of the kidney share the same genetics changes as conventional renal carcinoma. World J Urol 2004; 22: 120–123.

18.

Institute of Human Genetics, Helmholtz Centre Munich: Case control studies. Tests for deviation from Hardy-Weinberg equilibrium and tests for association. Munich: Institute of Human Genetics, Helmholtz Centre (available at: http://ihg2.helmholtz-muenchen.de/cgibin/hw/hwa1.pl).

19.

Calandra

Bernhagen

Mitchell

: The macrophage is an important and previously unrecognized source of macrophage migration inhibitory factor. J Exp Med 1994; 179: 1895–1902.

20.

Ogata

Nishihira

Suzuki

: Identification of macrophage migration inhibitory factor mRNA expression in neural cells of the rat brain by in situ hybridization. Neurosci Lett 1998; 246: 173–177.

21.

Nishihira

Koyama

Mizue

: Identification of macrophage migration inhibitory factor (MIF) in human vascular endothelial cells and its induction by lipopolysaccharide. Cytokine 1998; 10: 199–205.

22.

De Benedetti

Meazza

Vivarelli

: 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: 1398–1407.

23.

Martínez

Orozco

Varadé

: Macrophage migration inhibitory factor gene: Influence on rheumatoid arthritis susceptibility. Hum Immunol 2007; 68: 744–747.

24.

Amoli

Donn

Thomson

: Macrophage migration inhibitory factor gene polymorphism is associated with sarcoidosis in biopsy proven erythema nodosum. J Rheumatol 2002; 29: 1671–1673.

25.

Nohara

Okayama

Inoue

: Association of the −173G/C polymorphism of the macrophage migration inhibitory factor gene with ulcerative colitis. J Gastroenterol 2004; 39: 242–246.

26.

Hofstetter

Gold

Hartung

: Th17 cells in MS and experimental autoimmune encephalomyelitis. Int MS J 2009; 16: 12–18.

27.

Steinman

: Multiple sclerosis: A coordinated immunological attack against myelin in the central nervous system. Cell 1996; 85: 299–302.

28.

Mendel

de Rosbo

N Kerlero

Ben-Nun

: A myelin oligodendrocyte glycoprotein peptide induces typical chronic experimental autoimmune encephalomyelitis in H-2b mice: Fine specificity and T cell receptor Vβ expression of encephalitogenic T cells. Eur J Immunol 1995; 25: 1951–1959.

29.

Morand

: New therapeutic target in inflammatory disease: Macrophage migration inhibitory factor. Intern Med J 2005; 35: 419–426.

30.

Radstake

Sweep

Welsing

: Correlation of rheumatoid arthritis severity with the genetic functional variants and circulating levels of macrophage migration inhibitory factor. Arthritis Rheum 2005; 52: 3020–3029.

31.

Denkinger

Kort

: In vivo blockade of macrophage migration inhibitory factor ameliorates acute experimental autoimmune encephalomyelitis by impairing the homing of encephalitogenic T cells to the central nervous system. J Immunol 2003; 170: 1274–1282.

32.

Leech

Lacey

Xue

: Regulation of p53 by macrophage migration inhibitory factor in infammatory arthritis. Arthritis Rheum 2003; 48: 1881–1889.

33.

Bernhagen

Calandra

Mitchell

: MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature 1993; 365: 756–759.

34.

Vedder

Krieg

Gerlach

: Expression and glucocorticoid regulation of macrophage migration inhibitory factor (MIF) in hippocampal and neocortical rat brain cells in culture. Brain Res 2000; 869: 25–30.

35.

Calandra

Bernhagen

Metz

: MIF as a glucocorticoid-induced modulator of cytokine production. Nature 1995; 377: 68–71.

36.

Javeed

Zhao

: Macrophagemigration inhibitory factor: Role in inflammatory diseases and graft rejection. Inflamm Res 2008; 57: 45–50.

37.

Santos

Hall

Metz

: Role of macrophage migration inhibitory factor (MIF) in murine antigen-induced arthritis: Interaction with glucocorticoids. Clin Exp Immunol 2001; 123: 309–314.