Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations.
The human leukocyte antigen (HLA) DRB1*1501 has been consistently associated with multiple sclerosis (MS) in nearly all populations tested. This points to a specific antigen presentation as the pathogenic mechanism though this does not fully explain the disease association. The identification of exp...
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doaj-97e8f337d441499281c483ecd8062f4f2020-11-25T02:00:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0171e2981910.1371/journal.pone.0029819Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations.Antonio AlcinaMaría Del Mar Abad-GrauMaría FedetzGuillermo IzquierdoMiguel LucasOscar FernándezDorothy NdagireAntonio Catalá-RabasaAgustín RuizJavier GayánConcepción DelgadoCarmen ArnalFuencisla MatesanzThe human leukocyte antigen (HLA) DRB1*1501 has been consistently associated with multiple sclerosis (MS) in nearly all populations tested. This points to a specific antigen presentation as the pathogenic mechanism though this does not fully explain the disease association. The identification of expression quantitative trait loci (eQTL) for genes in the HLA locus poses the question of the role of gene expression in MS susceptibility. We analyzed the eQTLs in the HLA region with respect to MS-associated HLA-variants obtained from genome-wide association studies (GWAS). We found that the Tag of DRB1*1501, rs3135388 A allele, correlated with high expression of DRB1, DRB5 and DQB1 genes in a Caucasian population. In quantitative terms, the MS-risk AA genotype carriers of rs3135388 were associated with 15.7-, 5.2- and 8.3-fold higher expression of DQB1, DRB5 and DRB1, respectively, than the non-risk GG carriers. The haplotype analysis of expression-associated variants in a Spanish MS cohort revealed that high expression of DRB1 and DQB1 alone did not contribute to the disease. However, in Caucasian, Asian and African American populations, the DRB1*1501 allele was always highly expressed. In other immune related diseases such as type 1 diabetes, inflammatory bowel disease, ulcerative colitis, asthma and IgA deficiency, the best GWAS-associated HLA SNPs were also eQTLs for different HLA Class II genes. Our data suggest that the DR/DQ expression levels, together with specific structural properties of alleles, seem to be the causal effect in MS and in other immunopathologies rather than specific antigen presentation alone.http://europepmc.org/articles/PMC3258250?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Antonio Alcina María Del Mar Abad-Grau María Fedetz Guillermo Izquierdo Miguel Lucas Oscar Fernández Dorothy Ndagire Antonio Catalá-Rabasa Agustín Ruiz Javier Gayán Concepción Delgado Carmen Arnal Fuencisla Matesanz |
spellingShingle |
Antonio Alcina María Del Mar Abad-Grau María Fedetz Guillermo Izquierdo Miguel Lucas Oscar Fernández Dorothy Ndagire Antonio Catalá-Rabasa Agustín Ruiz Javier Gayán Concepción Delgado Carmen Arnal Fuencisla Matesanz Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations. PLoS ONE |
author_facet |
Antonio Alcina María Del Mar Abad-Grau María Fedetz Guillermo Izquierdo Miguel Lucas Oscar Fernández Dorothy Ndagire Antonio Catalá-Rabasa Agustín Ruiz Javier Gayán Concepción Delgado Carmen Arnal Fuencisla Matesanz |
author_sort |
Antonio Alcina |
title |
Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations. |
title_short |
Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations. |
title_full |
Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations. |
title_fullStr |
Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations. |
title_full_unstemmed |
Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations. |
title_sort |
multiple sclerosis risk variant hla-drb1*1501 associates with high expression of drb1 gene in different human populations. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2012-01-01 |
description |
The human leukocyte antigen (HLA) DRB1*1501 has been consistently associated with multiple sclerosis (MS) in nearly all populations tested. This points to a specific antigen presentation as the pathogenic mechanism though this does not fully explain the disease association. The identification of expression quantitative trait loci (eQTL) for genes in the HLA locus poses the question of the role of gene expression in MS susceptibility. We analyzed the eQTLs in the HLA region with respect to MS-associated HLA-variants obtained from genome-wide association studies (GWAS). We found that the Tag of DRB1*1501, rs3135388 A allele, correlated with high expression of DRB1, DRB5 and DQB1 genes in a Caucasian population. In quantitative terms, the MS-risk AA genotype carriers of rs3135388 were associated with 15.7-, 5.2- and 8.3-fold higher expression of DQB1, DRB5 and DRB1, respectively, than the non-risk GG carriers. The haplotype analysis of expression-associated variants in a Spanish MS cohort revealed that high expression of DRB1 and DQB1 alone did not contribute to the disease. However, in Caucasian, Asian and African American populations, the DRB1*1501 allele was always highly expressed. In other immune related diseases such as type 1 diabetes, inflammatory bowel disease, ulcerative colitis, asthma and IgA deficiency, the best GWAS-associated HLA SNPs were also eQTLs for different HLA Class II genes. Our data suggest that the DR/DQ expression levels, together with specific structural properties of alleles, seem to be the causal effect in MS and in other immunopathologies rather than specific antigen presentation alone. |
url |
http://europepmc.org/articles/PMC3258250?pdf=render |
work_keys_str_mv |
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