nach oben

Erschienen in:

01.11.2009

IL-2, IFN-γ, and IL-12 Gene Polymorphisms and Susceptibility to Multiple Sclerosis

verfasst von: Mohammad Ali Shokrgozar, Sheila Sarial, Aliakbar Amirzargar, Fazel Shokri, Nima Rezaei, Zohreh Arjang, Jalaledin Radfar, Manijeh Yousefi-behzadi, Mohammad Ali Sahraian, Jamshid Lotfi

Erschienen in: Journal of Clinical Immunology | Ausgabe 6/2009

Einloggen, um Zugang zu erhalten

Abstract

Background

Multiple sclerosis (MS) is a multifactorial disease. Positive genetic background could predispose individuals to this chronic disabling disease. In order to investigate the role of some proinflammatory cytokines (interleukin (IL)-2, IL-12, and interferon-gamma (IFN-γ)) as a risk factor for MS, this study was performed.

Methods

Two hundred and eleven patients with relapsing-remitting form of MS were enrolled in this study and compared with 359 healthy individuals. Using polymerase chain reaction based on sequence-specific primer method, the cytokine genes were amplified, and alleles and genotypes were detected on gel electrophoresis.

Results

Significant increases for IFN-γ AT (+874) genotype (54.5% vs. 37.8%, p = 0.0002) and IL-12 AA (−1188) genotype (60.8% vs. 49.7%, p = 0.014) were found in MS patients in comparison with healthy controls. A significant decrease in IFN-γ TT (+874) genotype (17.7% vs. 27.5%, p = 0.01) and IL-12 CA (–1188) genotype (30.9% vs. 45%, p = 0.001) in MS patients was also detected. No significant differences of IL-2 G/T (−330) and IL-2 G/T (+166) in alleles and genotypes were observed between MS patients and normal subjects.

Conclusions

It could be suggested that the genetic variation in IL-12 A/C (−1188) and IFN-γ A/T (+874) cytokine genes could be risk factors for MS patients.

Grigoriadis N, Grigoriadis S, Polyzoidou E, Milonas I, Karussis D. Neuroinflammation in multiple sclerosis: evidence for autoimmune dysregulation, not simple autoimmune reaction. Clin Neurol Neurosurg. 2006;108:241–4.CrossRefPubMed

Bidwell J, Keen L, Gallagher G, Kimberly R, Huizinga T, McDermott MF, et al. Cytokine gene polymorphism in human disease: on-line databases. Genes Immun. 1999;1:3–19.CrossRefPubMed

Bidwell J, Keen L, Gallagher G, Kimberly R, Huizinga T, McDermott MF, et al. Cytokine gene polymorphism in human disease: on-line databases, supplement 1. Genes Immun. 2001;2:61–70.CrossRefPubMed

Bidwell JL, Wood NA, Morse HR, Olomolaiye OO, Keen LJ, Laundy GJ. Human cytokine gene nucleotide sequence alignments: supplement 1. Eur J Immunogenet. 1999;26:135–223.CrossRefPubMed

Hollegaard MV, Bidwell JL. Cytokine gene polymorphism in human disease: on-line databases, Supplement 3. Genes Immun. 2006;7:269–76.CrossRefPubMed

Amirzargar AA, Bagheri M, Ghavamzadeh A, Alimoghadam K, Khosravi F, Rezaei N, et al. Cytokine gene polymorphism in Iranian patients with chronic myelogenous leukaemia. Int J Immunogenet. 2005;32:167–71.CrossRefPubMed

Amirzargar AA, Rezaei N, Jabbari H, Danesh AA, Khosravi F, Hajabdolbaghi M, et al. Cytokine single nucleotide polymorphisms in Iranian patients with pulmonary tuberculosis. Eur Cytokine Netw. 2006;17:84–9.PubMed

Mahdaviani SA, Rezaei N, Moradi B, Dorkhosh S, Amirzargar AA, Movahedi M. Proinflammatory cytokine gene polymorphisms among Iranian patients with asthma. J Clin Immunol. 2009;29:57–62.CrossRefPubMed

Rezaei N, Amirzargar AA, Shakiba Y, Mahmoudi M, Moradi B, Aghamohammadi A. Proinflammatory cytokine gene single nucleotide polymorphisms in common variable immunodeficiency. Clin Exp Immunol. 2009;155:21–7.CrossRefPubMed

10.

Amirzargar A, Mytilineos J, Yousefipour A, Farjadian S, Scherer S, Opelz G, et al. HLA class II (DRB1, DQA1 and DQB1) associated genetic susceptibility in Iranian multiple sclerosis (MS) patients. Eur J Immunogenet. 1998;25:297–301.CrossRefPubMed

11.

Amirzargar AA, Tabasi A, Khosravi F, Kheradvar A, Rezaei N, Naroueynejad M, et al. Optic neuritis, multiple sclerosis and human leukocyte antigen: results of a 4-year follow-up study. Eur J Neurol. 2005;12:25–30.CrossRefPubMed

12.

Amirzargar A, Khosravi F, Dianat S, Hushmand F, Maryousef P, Foroushani AR, et al. Profile of cytokine gene polymorphisms in Iranian multiple sclerosis patients. Mult Scler. 2007;13:253–5.CrossRefPubMed

13.

Sarial S, Shokrgozar MA, Amirzargar A, Shokri F, Radfar J, Zohrevand P, et al. IL-1, IL-1R and TNFalpha gene polymorphisms in Iranian patients with multiple sclerosis. Iran J Allergy Asthma Immunol. 2008;7:37–40.PubMed

14.

Hafler DA, Compston A, Sawcer S, Lander ES, Daly MJ, De Jager PL, et al. Risk alleles for multiple sclerosis identified by a genomewide study. N Engl J Med. 2007;357:851–62.CrossRefPubMed

15.

Baranzini SE, Galwey NW, Wang J, Khankhanian P, Lindberg R, Pelletier D, et al. Pathway and network-based analysis of genome-wide association studies in multiple sclerosis. Hum Mol Genet. 2009;18:2078–90.CrossRefPubMed

16.

McDonald WI, Compston A, Edan G, Goodkin D, Hartung HP, Lublin FD, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol. 2001;50:121–7.CrossRefPubMed

17.

Amirzargar AA, Naroueynejad M, Khosravi F, Dianat S, Rezaei N, Mytilineos J, et al. Cytokine single nucleotide polymorphisms in Iranian populations. Eur Cytokine Netw. 2008;19:104–12.PubMed

18.

Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.CrossRefPubMed

19.

Corcione A, Aloisi F, Serafini B, Capello E, Mancardi GL, Pistoia V, et al. B-cell differentiation in the CNS of patients with multiple sclerosis. Autoimmun Rev. 2005;4:549–54.CrossRefPubMed

20.

Hofstetter HH, Toyka KV, Gold R. Permanent effector phenotype of neuroantigen-specific T cells acquired in the central nervous system during experimental allergic encephalomyelitis. Neurosci Lett. 2006;391:127–30.CrossRefPubMed

21.

Kikuchi S, Niino M, Fukazawa T, Yabe I, Tashiro K. An assessment of the association between IL-2 gene polymorphisms and Japanese patients with multiple sclerosis. J Neurol Sci. 2002;205:47–50.CrossRefPubMed

22.

Zhang J, Markovic-Plese S, Lacet B, Raus J, Weiner HL, Hafler DA. Increased frequency of interleukin 2-responsive T cells specific for myelin basic protein and proteolipid protein in peripheral blood and cerebrospinal fluid of patients with multiple sclerosis. J Exp Med. 1994;179:973–84.CrossRefPubMed

23.

Matesanz F, Delgado C, Fresno M, Alcina A. Allelic selection of human IL-2 gene. Eur J Immunol. 2000;30:3516–21.CrossRefPubMed

24.

Matesanz F, Fedetz M, Collado-Romero M, Fernandez O, Guerrero M, Delgado C, et al. Allelic expression and interleukin-2 polymorphisms in multiple sclerosis. J Neuroimmunol. 2001;119:101–5.CrossRefPubMed

25.

Matesanz F, Fedetz M, Leyva L, Delgado C, Fernandez O, Alcina A. Effects of the multiple sclerosis associated −330 promoter polymorphism in IL2 allelic expression. J Neuroimmunol. 2004;148:212–7.CrossRefPubMed

26.

Matesanz F, Fernandez O, Alcina A. Genomewide study of multiple sclerosis. N Engl J Med. 2007;357:2200. author reply-1.PubMed

27.

Lees JR, Cross AH. A little stress is good: IFN-gamma, demyelination, and multiple sclerosis. J Clin Invest. 2007;117:297–9.CrossRefPubMed

28.

Imitola J, Chitnis T, Khoury SJ. Cytokines in multiple sclerosis: from bench to bedside. Pharmacol Ther. 2005;106:163–77.CrossRefPubMed

29.

Issazadeh S, Ljungdahl A, Hojeberg B, Mustafa M, Olsson T. Cytokine production in the central nervous system of Lewis rats with experimental autoimmune encephalomyelitis: dynamics of mRNA expression for interleukin-10, interleukin-12, cytolysin, tumor necrosis factor alpha and tumor necrosis factor. J Neuroimmunol. 1995;61:205–12.CrossRefPubMed

30.

Issazadeh S, Mustafa M, Ljungdahl A, Hojeberg B, Dagerlind A, Elde R, et al. Interferon gamma, interleukin 4 and transforming growth factor beta in experimental autoimmune encephalomyelitis in Lewis rats: dynamics of cellular mRNA expression in the central nervous system and lymphoid cells. J Neurosci Res. 1995;40:579–90.CrossRefPubMed

31.

Kantarci OH, Hebrink DD, Schaefer-Klein J, Sun Y, Achenbach S, Atkinson EJ, et al. Interferon gamma allelic variants: sex-biased multiple sclerosis susceptibility and gene expression. Arch Neurol. 2008;65:349–57.CrossRefPubMed

32.

Wansen K, Pastinen T, Kuokkanen S, Wikstrom J, Palo J, Peltonen L, et al. Immune system genes in multiple sclerosis: genetic association and linkage analyses on TCR beta, IGH, IFN-gamma and IL-1ra/IL-1 beta loci. J Neuroimmunol. 1997;79:29–36.CrossRefPubMed

33.

Mihailova S, Ivanova M, Mihaylova A, Quin L, Mikova O, Naumova E. Pro- and anti-inflammatory cytokine gene polymorphism profiles in Bulgarian multiple sclerosis patients. J Neuroimmunol. 2005;168:138–43.CrossRefPubMed

34.

Pravica V, Asderakis A, Perrey C, Hajeer A, Sinnott PJ, Hutchinson IV. In vitro production of IFN-gamma correlates with CA repeat polymorphism in the human IFN-gamma gene. Eur J Immunogenet. 1999;26:1–3.CrossRefPubMed

35.

Kang BY, Kim E, Kim TS. Regulatory mechanisms and their therapeutic implications of interleukin-12 production in immune cells. Cell Signal. 2005;17:665–73.CrossRefPubMed

36.

Campbell IL, Stalder AK, Akwa Y, Pagenstecher A, Asensio VC. Transgenic models to study the actions of cytokines in the central nervous system. Neuroimmunomodulation. 1998;5:126–35.CrossRefPubMed

37.

Alifirova VM, Orlova I, Babenko SA, Rudko AA, Puzyrev VP. The 1188 A/C ILI2B gene polymorphism in patients with multiple sclerosis and in healthy subjects of Tomsk region. Zh Nevrol Psikhiatr Im S S Korsakova. 2006;3:130–5.

38.

van Veen T, Crusius JB, Schrijver HM, Bouma G, Killestein J, van Winsen L, et al. Interleukin-12p40 genotype plays a role in the susceptibility to multiple sclerosis. Ann Neur. 2001;50(2):275.CrossRef

39.

Seegers D, Zwiers A, Strober W, Pena AS, Bouma G. A TaqI polymorphism in the 3′UTR of the IL-12 p40 gene correlates with increased IL-12 secretion. Genes Immun. 2002;3:419–23.CrossRefPubMed

40.

Hall MA, McGlinn E, Coakley G, Fisher SA, Boki K, Middleton D, et al. Genetic polymorphism of IL-12 p40 gene in immune-mediated disease. Genes Immun. 2000;1:219–24.CrossRefPubMed

41.

Martinez A, Varade J, Marquez A, Cenit MC, Espino L, Perdigones N, et al. Association of the STAT4 gene with increased susceptibility for some immune-mediated diseases. Arthritis Rheum. 2008;58:2598–602.CrossRefPubMed

Titel: IL-2, IFN-γ, and IL-12 Gene Polymorphisms and Susceptibility to Multiple Sclerosis
verfasst von: Mohammad Ali Shokrgozar
Sheila Sarial
Aliakbar Amirzargar
Fazel Shokri
Nima Rezaei
Zohreh Arjang
Jalaledin Radfar
Manijeh Yousefi-behzadi
Mohammad Ali Sahraian
Jamshid Lotfi
Publikationsdatum: 01.11.2009
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 6/2009
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-009-9310-z

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

IL-2, IFN-γ, and IL-12 Gene Polymorphisms and Susceptibility to Multiple Sclerosis