Nooshin Delfan; Mohammad Shafiei; Farideh Ghanbari-Mardasi; Tahereh Latifi; Nastaran Majdinasab; Tahereh Seifi
Volume 17, Issue 4 , December 2018, , Pages 154-160
Background: One of the demyelinating and inflammatory diseases of the central nervous system (CNS) is multiple sclerosis (MS). Though pathogenesis of MS is still unknown, both genetic and environmental factors are involved. The human leukocyte antigen (HLA) class-II alleles including HLA-DRB5*01, DQB1*0602, ...
Background: One of the demyelinating and inflammatory diseases of the central nervous system (CNS) is multiple sclerosis (MS). Though pathogenesis of MS is still unknown, both genetic and environmental factors are involved. The human leukocyte antigen (HLA) class-II alleles including HLA-DRB5*01, DQB1*0602, DRB1*1501, and DQA1*0102 may have remarkable effect in MS risk although it is controversial in studies. As there is no data with respect to the HLA-DRB1*1501-DRB5*01 correlation with MS in Khuzestan Province, Iran, the goal of the survey was to investigate the association of this haplotype with MS in this population.
Methods: The study focused on DRB5*01-DRB1*1501 haplotype association with MS in 200 patients and 200 healthy individuals. Typing of HLA was carried out by polymerase chain reaction (PCR) amplification with sequence-specific primers (SSP) method. SPSS software was used for the statistical analyses.
Results: No association between DRB5*01+-DRB1*1501+ and MS was found (P = 0.156). Distribution of DRB1*1501+-DRB5*01- (carrying DRB1*1501+ but not DRB5*01-) and DRB1*1501--DRB5*01- haplotypes was statistically different between patients and controls (29.73% vs. 11.81%, P < 0.001) and (42.16% vs. 68.50%, P < 0.001), respectively. However, DRB1*1501--DRB5*01+ revealed no association with MS (15.13% vs. 11.81%, P = 0.403). HLA-DRB1*1501--DRB5*01+ was signiﬁcantly more frequent among female patients with MS (16.19% vs. 6.12%, P = 0.019) and Persian group (17.11% vs. 5.79%, P = 0.027). Positive correlation of HLA-DRB1*1501+-DRB5*01- haplotype with the expanded disability status scale (EDSS) steps from 5 to 10 was observed (62.50% vs. 25.76%, P = 0.026). Moreover, no meaningful association was shown among the haplotypes with EDSS, course of MS, ethnicity, and gender.
Conclusion: Our findings suggest that DRB1*1501+-DRB5*01- and DRB1*1501--DRB5*01- haplotypes may have positive association with MS risk. Also, this survey indicates that HLA-DRB1*1501--DRB5*01+ is involved in susceptibility of the disease among women and Persians. DRB1*1501+-DRB5*01- genotype frequency may have a key role in MS developing.
Mahshid Hosseini Behbahani; Hamid Galehdari; Maryam Mohaghegh
Volume 13, Issue 3 , September 2014, , Pages 168-171
Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of central nervous system with unknown causes. Etiology of MS involves both genetic and environment factors. The interleukin 7 receptor (IL7R) gene ...
Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of central nervous system with unknown causes. Etiology of MS involves both genetic and environment factors. The interleukin 7 receptor (IL7R) gene is a promising candidate for MS, because its involvement in the autoimmunity, regulation of the T-cell homeostasis, proliferation, and anti-apoptotic signaling.Methods: We investigated the association of the IL7R gene polymorphism rs6897932 in MS patients in a case and control study. In this case and control study participating, 127 relapsing-remitting MS (RRMS) patients (mean age: 32.25, age range: 16-57) selected according McDonald criteria, and 109 ethnically, sex and age matched healthy control (mean age: 27.44, age range: 14-63) with no personal or family history of autoimmune diseases were studied. DNA was extracted from whole blood using high pure polymerase chain reaction template preparatio kit from Roch Company. Amplification refractory mutation system method was applied to define the genotyping C/T within exon 6 of the IL7R gene among individuals.Results: Evaluation of the IL7R gene polymorphism revealed that the T allele and the C/T and T/T genotypes are present in 53.5%, 42.5%, 4.0%, and 68.8%, 26.6%, 4.6% in MS patients and controls, respectively. Comparison between alleles and genotypes in the MS patients and healthy controls show significant differences (P = 0.038).Conclusion: The distribution of the rs6897932 polymorphism is significantly different in our case/control study in Khuzestan Province. This single nucleotide polymorphism causes alternative splicing in exon 6 of the IL7R gene with possible influence of the autoimmunity.