Abstract
Multiple sclerosis (MS) is a central nervous system (CNS) demyelinating disease characterized
by a relapsing–remitting course leading to progressive disability. Given the critical
role of apoptosis-related genes in the maintenance of homeostasis in the immune privilege
sites, mutations in these genes have a profound effect on occurring autoimmune diseases
such as multiple sclerosis. In the current study, polymorphisms in the apoptosis-related
genes: Fas _-670 A>G, FasL _-844C>T, FasLIVS2nt _124 A>G and TRAIL_1595C>T were analyzed in 107 Iranian patients suffering
from MS and 112 unrelated healthy controls using PCR-RFLP method. Our results demonstrated
that among Iranian patients with MS and controls being homozygous in Fas_670A/A, G/G
and FasL_-844C/C, TT in the promoter region and homozygocity in the minor allele for
FasLIVS2nt_124G/G and TRAIL_1595C/C, polymorphisms were not associated with the MS
risk in Iranian patients when compared with normal controls. However, the Fas _-670G/G
genotype had a borderline significantly increased frequency with secondary progressive
MS type (X2=5.8, P=0.05). In conclusion, no statistical association was found between the Fas, FasL and
TRAIL polymorphisms and the risk of MS in Iranian patients.
Abbreviations:
TRAIL (TNF Related Apoptosis Inducing Ligand), PCR (Polymerase Chain Reaction), RFLP (Restriction Fragment Length Polymorphism)Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of the Neurological SciencesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Impaired apoptosis in mitogen-stimulated lymphocytes of patients with multiple sclerosis.Neuroreport. 1999; 10: 399-402
- Genetically determined failure of activation-induced apoptosis of autoreactive T cells as a cause of multiple sclerosis.Lancet. 1998; 351: 978-981
- Fas(t) track to apoptosis in MS: TNF receptors may suppress or potentiate CNS demyelination.Neurology. 2000; 55: 906-907
- Impaired apoptotic deletion of myelin basic protein-reactive T cells in patients with multiple sclerosis.Eur J Immunol. 1999; 29: 1692-1700
- Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family.Cell. 1993; 75: 1169-1178
- The Fas signaling pathway: more than a paradigm.Science. 2002; 296: 1635-1636
- Functional FAS promoter polymorphisms are associated with increased risk of acute myeloid leukemia.Cancer Res. 2003; 63: 4327-4330
- A novel polymorphic CAAT/enhancer-binding protein beta element in the FasL gene promoter alters Fas ligand expression: a candidate background gene in African American systemic lupus erythematosus patients.J Immunol. 2003; 170: 132-138
- Isolation and molecular characterization of the 5′-upstream region of the human TRAIL gene.Biochem Biophys Res Commun. 2000; 276: 466-471
- Three polymorphisms in the 3′ UTR of the TRAIL (TNF-related apoptosis-inducing ligand) gene.Genes Immun. 2001; 2: 469-470
- Immune (dys)regulation in multiple sclerosis: role of the CD95-CD95 ligand system.Immunol Today. 1999; 20: 550-554
- TRAIL/Apo-2-ligand-induced apoptosis in human T cells.Eur J Immunol. 1998; 28: 143-152
- Surface expression of TRAIL/Apo-2 ligand in activated mouse T and B cells.Eur J Immunol. 1998; 28: 1492-1498
- Upregulation of the apoptosis regulators cFLIP, CD95 and CD95 ligand in peripheral blood mononuclear cells in relapsing–remitting multiple sclerosis.J Neuroimmunol. 2003; 135: 126-134
- New diagnostic criteria for multiple sclerosis: guidelines for research protocols.Ann Neurol. 1983; 13: 227-231
- Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis.Ann Neurol. 2001; 50: 121-127
- Fas and Fas ligand gene polymorphisms in primary Sjogren's syndrome.J Rheumatol. 2000; 27: 2397-2405
- A polymorphism in FAS gene promoter associated with increased risk of nasopharyngeal carcinoma and correlated with anti-nuclear autoantibodies induction.Cancer Lett. 2006; 233: 21-27
- Fas ligand gene polymorphisms are not associated with Hashimoto's thyroiditis and Graves' disease.Hum Immunol. 2003; 64: 285-289
- TNF-related apoptosis inducing ligand (TRAIL) gene polymorphism in Japanese patients with multiple sclerosis.J Neuroimmunol. 2005; 167: 170-174
- Involvement of the CD95 (APO-1/Fas) receptor/ligand system in multiple sclerosis brain.J Exp Med. 1996; 184: 1513-1518
- Homeostasis of naive and memory CD4+ T cells: IL-2 and IL-7 differentially regulate the balance between proliferation and Fas-mediated apoptosis.J Immunol. 2003; 171: 61-68
- Regulatory T cells control autoimmunity in vivo by inducing apoptotic depletion of activated pathogenic lymphocytes.J Immunol. 2003; 170: 2985-2992
- Regulatory effects of cytokines and cyclosporine A on peripheral blood mononuclear cells from stable multiple sclerosis patients.Immunopharmacol Immunotoxicol. 1999; 21: 527-549
- Identification and characterization of polymorphisms in the promoter region of the human Apo-1/Fas (CD95) gene.Mol Immunol. 1997; 34: 577-582
- Apoptosis mediators fasL and TRAIL are upregulated in peripheral blood mononuclear cells in MS.Neurology. 2000; 55: 928-934
Article info
Publication history
Published online: August 24, 2011
Accepted:
July 21,
2011
Received in revised form:
June 1,
2011
Received:
May 5,
2010
Identification
Copyright
© 2011 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
