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Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
High frequency of the IL-2 -330 T/HLA-DRB1*1501 haplotype in patients with multiple sclerosis
Majid Shahbazi1, Danial Roshandel, Hamid Ebadi
1Medical Cellular & Molecular Research Center, Talghani Children Hospital of Golestan University of Medical Sciences, Bolv Janbazan, 4916668197, Gorgan, Iran. shahbazimajid@yahoo.co.uk
Abstract:
We have evaluated the role of the HLA-DRB1*1501 allele and the IL-2 -330 T/G polymorphism and their interaction in susceptibility to multiple sclerosis on 360 patients and 426 matched healthy individuals. We used the SSP-PCR method to determine the alleles. Fisher's exact test was used to analyses. We observed a significant increase in the T allele at IL-2 -330 position in patients (OR=1.34, P<0.05), and the T/T and T/G genotypes were more frequent among patients than controls. The HLA-DRB1*1501 allele was overrepresented in patients as compared to the control group (OR=1.7, P=0.0006). The two-locus analysis of the interaction between the IL-2 promoter polymorphism and the HLA-DRB1 allele showed that the HLA-DRB1*1501/T haplotype was more frequent in patients than controls (OR=16, P<0.0001). Our findings support previous findings about the role of the HLA-DRB1*1501 allele in susceptibility to MS. This work also provides new findings about the importance of gene-gene interactions in the development of MS.
Insights
This study reveals that the HLA-DRB1*1501 allele and the IL-2 -330 T allele significantly increase multiple sclerosis risk. Gene-gene interactions, particularly the HLA-DRB1*1501/T haplotype, are crucial in multiple sclerosis development.
Area of Science:
- Immunogenetics
- Neuroimmunology
- Human Genetics
Background:
- Multiple sclerosis (MS) is a complex autoimmune disease affecting the central nervous system.
- Genetic factors, including human leukocyte antigen (HLA) genes and cytokine polymorphisms, are implicated in MS susceptibility.
- The role of specific alleles and their interactions in MS pathogenesis requires further elucidation.
Purpose of the Study:
- To investigate the association of the HLA-DRB1*1501 allele and the Interleukin-2 (IL-2) -330 T/G polymorphism with multiple sclerosis risk.
- To examine the potential gene-gene interaction between HLA-DRB1*1501 and IL-2 -330 polymorphism in MS susceptibility.
Main Methods:
- Case-control study involving 360 MS patients and 426 healthy controls.
- Genotyping of HLA-DRB1*1501 allele and IL-2 -330 T/G polymorphism using SSP-PCR.
- Statistical analysis using Fisher's exact test and logistic regression for odds ratio (OR) and P-values.
Main Results:
- The IL-2 -330 T allele was significantly more frequent in MS patients (OR=1.34, P<0.05), with T/T and T/G genotypes also increased.
- The HLA-DRB1*1501 allele was significantly overrepresented in patients (OR=1.7, P=0.0006).
- A strong interaction was observed, with the HLA-DRB1*1501/T haplotype showing a markedly higher frequency in patients (OR=16, P<0.0001).
Conclusions:
- The findings confirm the association of HLA-DRB1*1501 with multiple sclerosis susceptibility.
- This study highlights the significant role of gene-gene interactions, specifically involving the IL-2 promoter polymorphism and HLA-DRB1*1501, in the development of MS.
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