ArticleMultiple sclerosis (Houndmills, Basingstoke, England)2019
Deconstruction of HLA-DRB1*04:01:01 and HLA-DRB1*15:01:01 class II haplotypes using next-generation sequencing in European-Americans with multiple sclerosis.
Article in Multiple sclerosis (Houndmills, Basingstoke, England), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- High Resolution Haplotype Analyses of Classical HLA Genes in Families With Multiple Sclerosis Highlights the Role of HLA-DP Alleles in Disease Susceptibility.Frontiers in immunology · 2021Trial
- HLA polymorphism in neuroimmune diseases: linking antigen presentation to neuroinflammatory programs.Frontiers in immunology · 2026Review
- Immunogenetics of Multiple Sclerosis in Romanian Patients: Preliminary Data.International journal of molecular sciences · 2025Article
- HLA-DQB1*05 subtypes and not DRB1*10:01 mediates risk in anti-IgLON5 disease.Brain : a journal of neurology · 2024Article
- Blood immunophenotyping of multiple sclerosis patients at diagnosis identifies a classical monocyte subset associated to disease evolution.Frontiers in immunology · 2024Article
- Article
- High-resolution HLA allele and haplotype frequencies in several unrelated populations determined by next generation sequencing: 17th International HLA and Immunogenetics Workshop joint report.Human immunology · 2021Article
- Altered Immune Phenotypes andFrontiers in immunology · 2021Article
- Next-Generation Sequencing Identifies Extended HLA Class I and II Haplotypes Associated With Early-Onset and Late-Onset Myasthenia Gravis in Italian, Norwegian, and Swedish Populations.Frontiers in immunology · 2021Article
- Genetic Analyses of Common Infections in the Avon Longitudinal Study of Parents and Children Cohort.Frontiers in immunology · 2021Article
- HLA Class II Genotype Does Not Affect the Myelin Responsiveness of Multiple Sclerosis Patients.Cells · 2020Article
- Genomic, proteomic, and systems biology approaches in biomarker discovery for multiple sclerosis.Cellular immunology · 2020Review
- Next-generation sequencing reveals new information about HLA allele and haplotype diversity in a large European American population.Human immunology · 2019Article
- Report from the Killer-cell Immunoglobulin-like Receptors (KIR) component of the 17th International HLA and Immunogenetics Workshop.Human immunology · 2018Article
- Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe association between HLA-DRB1*15:01 with multiple sclerosis (MS) susceptibility is well established, but the contribution of the tightly associated HLA-DRB5*01:01 allele has not yet been completely ascertained. Similarly, the effects of HLA-DRB1*04:01 alleles and haplotypes, defined at the full-gene resolution level with MS risk remains to be elucidated.
objectivesTo characterize the molecular architecture of class II HLA-DR15 and HLA-DR4 haplotypes associated with MS.
methodsNext-generation sequencing was used to determine HLA-DQB1, HLA-DQA1, and HLA-DRB1/4/5 alleles in 1403 unrelated European-American patients and 1425 healthy unrelated controls. Effect sizes of HLA alleles and haplotypes on MS risk were measured by odds ratio (OR) with 95% confidence intervals.
resultsHLA-DRB1*15:01:01:01SG (OR = 3.20, p < 2.2E-16), HLA-DRB5*01:01:01 (OR = 2.96, p < 2.2E-16), and HLA-DRB5*01:01:01v1_STR1 (OR = 8.18, p = 4.3E-05) alleles all occurred at significantly higher frequencies in MS patients compared to controls. The most significant predis-posing haplotypes were HLA-DQB1*06:02:01~ HLA-DQA1*01:02:01:01SG~HLA-DRB1*15:01:01:01SG~HLA-DRB5*01:01:01 and HLA-DQB1*06:02:01~HLA-DQA1*01:02:01:01SG~HLA-DRB1*15:01:01:01SG~HLA-DRB5*01:01:01v1_STR1 (OR = 3.19, p < 2.2E-16; OR = 9.30, p = 9.7E-05, respectively). Analyses of the HLA-DRB1*04 cohort in the absence of HLA-DRB1*15:01 haplotypes revealed that the HLA-DQB1*03:01:01:01~HLA-DQA1*03:03:01:01~HLA-DRB1*04:01:01:01SG~HLA-DRB4*01:03:01:01 haplotype was protective (OR = 0.64, p = 0.028), whereas the HLA-DQB1*03:02:01~HLA-DQA1*03:01:01~HLA-DRB1*04:01:01:01SG~HLA-DRB4*01:03:01:01 haplotype was associated with MS susceptibility (OR = 1.66, p = 4.9E-03).
conclusionHLA-DR15 haplotypes, including genomic variants of HLA-DRB5, and HLA-DR4 haplotypes affect MS risk.
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