RT Journal Article
T1 Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations.
A1 Alcina, Antonio
A1 Fedetz, María
A1 Izquierdo, Guillermo
A1 Lucas, Miguel
A1 Fernández, Oscar
A1 Ndagire, Dorothy
A1 Catalá-Rabasa, Antonio
A1 Ruiz, Agustín
A1 Gayán, Javier
A1 Delgado, Concepción
A1 Arnal, Carmen
A1 Matesanz, Fuencisla
K1 Adulto
K1 Alelos
K1 Grupo de Ascendencia Continental Europea
K1 Femenino
K1 Regulación de la Expresión Génica
K1 Estudios de Asociación Genética
K1 Predisposición Genética a la Enfermedad
K1 Genética de Población
K1 Estudio de Asociación del Genoma Completo
K1 Cadenas beta de HLA-DQ
K1 Cadenas HLA-DRB1
K1 Cadenas HLA-DRB5
K1 Haplotipos
K1 Humanos
K1 Desequilibrio de Ligamiento
K1 Modelos Logísticos
K1 Masculino
K1 Esclerosis Múltiple
K1 Polimorfismo de Nucleótido Simple
K1 Sitios de Carácter Cuantitativo
AB 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.
PB Public Library of Science
PB Francesc Palau, Instituto de Ciencia de Materiales de Madrid - Instituto de Biomedicina de Valencia, Spain
YR 2012
FD 2012-01-13
LK http://hdl.handle.net/10668/828
UL http://hdl.handle.net/10668/828
LA en
NO Alcina A, Abad-Grau Mdel M, Fedetz M, Izquierdo G, Lucas M, Fernández O, et al. Multiple sclerosis risk variant HLA-DRB1*1501 associates with high expression of DRB1 gene in different human populations. PLoS ONE; 7(1):e29819
DS RISalud
RD Feb 14, 2025