HLA-DRB1*15:01 and multiple sclerosis: a female association?

Background: The association between multiple sclerosis (MS) and the HLA-DRB1*15: 01 haplotype has been proven to be strong, but its molecular basis remains unclear. Vitamin D receptor (VDR) gene variants and sex have been proposed to modulate this association. Objectives: 1) Test the association of...

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Autores: Irizar, Haritz, Muñoz Culla, Maider, Zuriarrain, Olaia, Goyenechea Soto, Estibaliz, Castillo Triviño, Tamara, Prada, Alvaro, Sáenz Cuesta, Matías, De Juan, Dolores, López de Munain Arregui, Adolfo José, Olascoaga, Javier, Otaegui Bichot, David
Tipo de recurso: artículo
Fecha de publicación:2011
País:España
Institución:Universidad del País Vasco
Repositorio:Addi. Archivo Digital para la Docencia y la Investigación
OAI Identifier:oai:addi.ehu.eus:10810/65045
Acceso en línea:http://hdl.handle.net/10810/65045
Access Level:acceso abierto
Palabra clave:HLA-DRB1*15:01
HLA II gene expression
multiple sclerosis
sex
VDR
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spelling HLA-DRB1*15:01 and multiple sclerosis: a female association?Irizar, HaritzMuñoz Culla, MaiderZuriarrain, OlaiaGoyenechea Soto, EstibalizCastillo Triviño, TamaraPrada, AlvaroSáenz Cuesta, MatíasDe Juan, DoloresLópez de Munain Arregui, Adolfo JoséOlascoaga, JavierOtaegui Bichot, DavidHLA-DRB1*15:01HLA II gene expressionmultiple sclerosissexVDRBackground: The association between multiple sclerosis (MS) and the HLA-DRB1*15: 01 haplotype has been proven to be strong, but its molecular basis remains unclear. Vitamin D receptor (VDR) gene variants and sex have been proposed to modulate this association. Objectives: 1) Test the association of MS with *15:01 and VDR variants; 2) check whether VDR variants and/or sex modulate the risk conferred by *15:01; 3) study whether *15:01, VDR variants and/or sex affect HLA II gene expression. Methods: Peripheral blood from 364 MS patients and 513 healthy controls was obtained and DNA and total RNA were extracted from leukocytes. HLA-DRB1, DRB5 and DQA1 gene expression measurements and *15:01 genotyping were performed by qPCR. VDR variants were genotyped by PCR-RFLP. Results: Our data confirms that the *15:01 haplotype confers a higher risk of suffering from MS (OR = 1.364; 95% CI = 1.107-1.681). No association was found between VDR variants and MS, but they were shown to moderately modulate the risk conferred by *15:01. Sex confers a much stronger modulation and the *15:01-MS association seems to be female specific. A higher *15:01 frequency has been observed in Basques (45.1%). *15:01 positive samples showed a significant overexpression of DRB1 (p < 0.001), DRB5 (p < 0.001) and DQA1 (p = 0.004) in patients. DRB1 (p = 0.004) and DRB5 (p < 0.001) were also overexpressed in *15:01 controls. Conclusions: We confirm the *15:01-MS association and support that it is female specific. The relevance of ethnic origin on association studies has also been highlighted. HLA-DRB1*15:01 seems to be a haplotype consistently linked to high HLA II gene expression.This work was supported by the Basque Government (grant numbers BFI09.294 to HI and BFI09.206 to MMC), Rio-Hortega (grant number CM09/00129 to TC), the Ilundain Fundazioa, and Fundación 2000 and FIS (grant number PS09/02105).Sage202420242011info:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10810/65045reponame:Addi. Archivo Digital para la Docencia y la Investigacióninstname:Universidad del País VascoIngléshttps://journals.sagepub.com/doi/10.1177/1352458511426813info:eu-repo/semantics/openAccess© The Author(s) 2012 published by Sageoai:addi.ehu.eus:10810/650452026-06-18T09:23:17Z
dc.title.none.fl_str_mv HLA-DRB1*15:01 and multiple sclerosis: a female association?
title HLA-DRB1*15:01 and multiple sclerosis: a female association?
spellingShingle HLA-DRB1*15:01 and multiple sclerosis: a female association?
Irizar, Haritz
HLA-DRB1*15:01
HLA II gene expression
multiple sclerosis
sex
VDR
title_short HLA-DRB1*15:01 and multiple sclerosis: a female association?
title_full HLA-DRB1*15:01 and multiple sclerosis: a female association?
title_fullStr HLA-DRB1*15:01 and multiple sclerosis: a female association?
title_full_unstemmed HLA-DRB1*15:01 and multiple sclerosis: a female association?
title_sort HLA-DRB1*15:01 and multiple sclerosis: a female association?
dc.creator.none.fl_str_mv Irizar, Haritz
Muñoz Culla, Maider
Zuriarrain, Olaia
Goyenechea Soto, Estibaliz
Castillo Triviño, Tamara
Prada, Alvaro
Sáenz Cuesta, Matías
De Juan, Dolores
López de Munain Arregui, Adolfo José
Olascoaga, Javier
Otaegui Bichot, David
author Irizar, Haritz
author_facet Irizar, Haritz
Muñoz Culla, Maider
Zuriarrain, Olaia
Goyenechea Soto, Estibaliz
Castillo Triviño, Tamara
Prada, Alvaro
Sáenz Cuesta, Matías
De Juan, Dolores
López de Munain Arregui, Adolfo José
Olascoaga, Javier
Otaegui Bichot, David
author_role author
author2 Muñoz Culla, Maider
Zuriarrain, Olaia
Goyenechea Soto, Estibaliz
Castillo Triviño, Tamara
Prada, Alvaro
Sáenz Cuesta, Matías
De Juan, Dolores
López de Munain Arregui, Adolfo José
Olascoaga, Javier
Otaegui Bichot, David
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv HLA-DRB1*15:01
HLA II gene expression
multiple sclerosis
sex
VDR
topic HLA-DRB1*15:01
HLA II gene expression
multiple sclerosis
sex
VDR
description Background: The association between multiple sclerosis (MS) and the HLA-DRB1*15: 01 haplotype has been proven to be strong, but its molecular basis remains unclear. Vitamin D receptor (VDR) gene variants and sex have been proposed to modulate this association. Objectives: 1) Test the association of MS with *15:01 and VDR variants; 2) check whether VDR variants and/or sex modulate the risk conferred by *15:01; 3) study whether *15:01, VDR variants and/or sex affect HLA II gene expression. Methods: Peripheral blood from 364 MS patients and 513 healthy controls was obtained and DNA and total RNA were extracted from leukocytes. HLA-DRB1, DRB5 and DQA1 gene expression measurements and *15:01 genotyping were performed by qPCR. VDR variants were genotyped by PCR-RFLP. Results: Our data confirms that the *15:01 haplotype confers a higher risk of suffering from MS (OR = 1.364; 95% CI = 1.107-1.681). No association was found between VDR variants and MS, but they were shown to moderately modulate the risk conferred by *15:01. Sex confers a much stronger modulation and the *15:01-MS association seems to be female specific. A higher *15:01 frequency has been observed in Basques (45.1%). *15:01 positive samples showed a significant overexpression of DRB1 (p < 0.001), DRB5 (p < 0.001) and DQA1 (p = 0.004) in patients. DRB1 (p = 0.004) and DRB5 (p < 0.001) were also overexpressed in *15:01 controls. Conclusions: We confirm the *15:01-MS association and support that it is female specific. The relevance of ethnic origin on association studies has also been highlighted. HLA-DRB1*15:01 seems to be a haplotype consistently linked to high HLA II gene expression.
publishDate 2011
dc.date.none.fl_str_mv 2011
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/10810/65045
url http://hdl.handle.net/10810/65045
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://journals.sagepub.com/doi/10.1177/1352458511426813
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
© The Author(s) 2012 published by Sage
eu_rights_str_mv openAccess
rights_invalid_str_mv © The Author(s) 2012 published by Sage
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Sage
publisher.none.fl_str_mv Sage
dc.source.none.fl_str_mv reponame:Addi. Archivo Digital para la Docencia y la Investigación
instname:Universidad del País Vasco
instname_str Universidad del País Vasco
reponame_str Addi. Archivo Digital para la Docencia y la Investigación
collection Addi. Archivo Digital para la Docencia y la Investigación
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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