Background & objectives
Analysis of the role of different alleles of human leukocyte antigen (HLA) in multiple sclerosis (MS) patients is necessary in many populations and geographical areas. The aim of the present study was to investigate the frequency of HLA-DRB1 genes and its influence on susceptibility to MS, comparing with that in control group.
Design and setting
Two groups of case–control of multiple sclerosis patients referred to clinic at Khatam hospitals were studied. The first group consisted of 73 multiple sclerosis patients and the second group comprised 40 healthy volunteers with no known history of MS, living in Tehran.
Patients and methods
The sample population consisted of 73 consecutive non-selected patients diagnosed with MS according to the McDonald criteria (2010) at the outpatient clinic for multiple sclerosis, 62 (85%) presented with RRMS and 11 (15%) with SPMS. The frequency of HLA-DRB1 alleles was determined in 73 MS patients (with age of 18–56) and 40 healthy subjects in Iran. These consisted of 57 females and 16 males. HLA-DRB1 allele types were identified by polymerase chain reaction products of 24 pair primers for low resolution SSP typing (PCR-SSP).
The HLA-DRB1* 11/15 genotype was detected highest (6 times) in patients compare to normal control population (p-value 0.062), whereas the DRB1 4/11 genotype was detected highest (4 times) in controls compare to MS patients (p-value 0.033). The data showed that HLA-DRB1*03 is significantly more in patients compare to control normal people (p-value 0.0021) as well as DRB1 14 and 16 are significantly more in control normal people, compare to MS patients (p-values 0.0789 and 0.035).
Allele frequency among patients with positive history of multiple sclerosis disease showed that DRB1 11 allele has a significantly low rate in MS patients with positive history compare to other patients. In contrast DRB1 15 allele has a significantly high rate in MS patients with positive history compare to other patients. The frequencies of other alleles were not significantly different between the MS patients and the control group. The frequency of the HLA-DRB1* 11/15 genotype detected in the present study showed that this genotype is partially significant factor for MS susceptibility and development in Iran.
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 access
One-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 Sciences
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Ethnicity-dependent association of HLA DRB1-DQA1-DQB1 alleles in Brazilian multiple sclerosis patients.Acta Neurol Scand. 2007; 115: 306-311
- The importance of HLA DRB1 gene allele to clinical features and disability in patients with multiple sclerosis in Lithuania.BMC Neurol. 2013; 13: 77
- Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosis.Hum Mol Genet. 2006; 15: 2813-2824
- Development of biomarkers in multiple sclerosis.Brain. 2004; 127: 1463-1478
- HLA-A confers an HLA-DRB1 independent influence on the risk of multiple sclerosis.PLoS One. 2007; 2: e664
- Sex steroid regulation of microglial cell activation: relevance to multiple sclerosis.Ann N Y Acad Sci. 2003; 1007: 329-334
- TCR beta polymorphisms and multiple sclerosis.Genes Immun. 2004; 5: 337-342
- Genetic epidemiology of multiple sclerosis.Curr Opin Neurol. 1996; 9: 55-158
- Analysis of HLA DR2&DQ6 (DRB1*1501, DQA1*0102, DQB1*0602) haplotypes in Iranian patients with multiple sclerosis.Cell Mol Neurobiol. 2009; 29: 109-114
- Risk for multiple sclerosis in relatives and spouses of patients diagnosed with autoimmune and related conditions.Neurogenetics. 2009; 10: 5-11
- HLA-DR 15 is associated with female sex and younger age at diagnosis in multiple sclerosis.J Neurol Neurosurg Psychiatry. 2002; 72: 184-187
- HLA-DRB1* allele-associated genetic susceptibility and protection against multiple sclerosis in Brazilian patients.Mol Med Rep. 2009; 2: 993-998
- Histocompatibility antigen (HLA) associations with multiple sclerosis in Iran.Mult Scler. 2000; 6: 317-319
- HLA associations with multiple sclerosis in Greece.J Neurol Sci. 2011; 308: 28-31
- Histocompatibility antigens (HLA) in multiple sclerosis in Iran.J Neurol Neurosurg Psychiatry. 1978; 41: 699-701
- Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis.Neurology. 1996; 46: 907-911
- Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of Multiple Sclerosis.Ann Neurol. 2001; 50: 121-127
- Key issues in the diagnosis and treatment of multiple sclerosis. An overview.Neurology. 2002; 59: S1-S33
- Selection for T-cell receptor V beta-D beta-J beta gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis.Nature. 1993; 362: 68-70
- Genotype–phenotype correlations in multiple sclerosis: HLA genes influence disease severity inferred by 1HMR spectroscopy and MRI measures.Brain. 2009; 132: 250-259
- Diagnostic criteria for multiple sclerosis: 2005 revisions to the “McDonald Criteria”.Ann Neurol. 2005; 58: 840-846
- HLA-DRB1: genetic susceptibility and disability progression in a Spanish multiple sclerosis population.Eur J Neurol. 2011; 18: 337-342
- The detection of HLA-DR MB and MT determinants on purified class II molecules by inhibition of microcytotoxicity.J Immunol Methods. 1984; 73: 387-399
- The impact of HLA-A and -DRB1 on age at onset, disease course and severity in Scandinavian multiple sclerosis patients.Eur J Neurol. 2007; 14: 835-840
- Immunology of multiple sclerosis.Annu Rev Immunol. 2005; 23: 683-747
- Heterogeneity at the HLA-DRB1 allelic variation locus does not influence multiple sclerosis disease severity, brain atrophy or cognition.Mult Scler. 2011; 17: 344-352
- Modifying effects of HLA-DRB1 allele interactions on age at onset of multiple sclerosis in Western Australia.Mult Scler. 2010; 16: 15-20
Published online: July 16, 2014
Accepted: July 7, 2014
Received in revised form: April 30, 2014
Received: March 5, 2014
© 2014 Elsevier B.V. Published by Elsevier Inc. All rights reserved.