Association of HLA-G 3 ' untranslated region variants with type 1 diabetes mellitus
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1016/j.humimm.2016.02.001 http://hdl.handle.net/11449/161444 |
Resumo: | Besides the well recognized association of HLA-DRB1 and DQB1 alleles with type 1 diabetes mellitus (T1D), linkage studies have identified a gene region close to the non-classical class I HLA-G gene as an independent susceptibility marker. HLA-G is constitutively expressed in the endocrine compartment of the human pancreas and may play a role in controlling autoimmune responses. We evaluated the genetic diversity of the 3' untranslated region (3'UTR) of HLA-G, which have been associated with HLA-G mRNA post-transcriptional regulation, in 120 Brazilian T1D patients and in 120 healthy controls. We found the +3001 T allele was observed only in T1D patients. Notably, the +3001 T allele was in linkage disequilibrium with polymorphic sites associated with low production of HLA-G mRNA or soluble HLA-G levels. Moreover, T1D patients showed a low frequency of the HLA-G 3'UTR-17 (14bpINS/+3001T/+3003T/+30 10C/+3027C/+3035T/+3142G/+3187A/+3196C). The +3010 CC genotype and the UTR-3 haplotype (14bp DEL/+3001C/+3003T/+3010C/+3027C/+3035C/+3142G/+3187A/+3196C), associated with low and moderate soluble HLA-G expression, respectively, were underrepresented in patients. The decreased expression of HLA-G at the pancreas level should be detrimental in individuals genetically prone to produce less HLA-G. (C) 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. |
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Association of HLA-G 3 ' untranslated region variants with type 1 diabetes mellitusType 1 diabetes mellitusHLA-G3 ' untranslated regionGene regulationBraziliansBesides the well recognized association of HLA-DRB1 and DQB1 alleles with type 1 diabetes mellitus (T1D), linkage studies have identified a gene region close to the non-classical class I HLA-G gene as an independent susceptibility marker. HLA-G is constitutively expressed in the endocrine compartment of the human pancreas and may play a role in controlling autoimmune responses. We evaluated the genetic diversity of the 3' untranslated region (3'UTR) of HLA-G, which have been associated with HLA-G mRNA post-transcriptional regulation, in 120 Brazilian T1D patients and in 120 healthy controls. We found the +3001 T allele was observed only in T1D patients. Notably, the +3001 T allele was in linkage disequilibrium with polymorphic sites associated with low production of HLA-G mRNA or soluble HLA-G levels. Moreover, T1D patients showed a low frequency of the HLA-G 3'UTR-17 (14bpINS/+3001T/+3003T/+30 10C/+3027C/+3035T/+3142G/+3187A/+3196C). The +3010 CC genotype and the UTR-3 haplotype (14bp DEL/+3001C/+3003T/+3010C/+3027C/+3035C/+3142G/+3187A/+3196C), associated with low and moderate soluble HLA-G expression, respectively, were underrepresented in patients. The decreased expression of HLA-G at the pancreas level should be detrimental in individuals genetically prone to produce less HLA-G. (C) 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fundacao de Apoio ao Ensino Pesquisa e Assistencia (FAEPA)Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Genet, Av Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP, BrazilIst Sci San Raffaele, San Raffaele Telethon Inst Gene Therapy HSR TIGET, Div Regenerat Med Stem Cells & Gene Therapy, I-20132 Milan, ItalyUniv Sao Paulo, Fac Filosofia Ciencias & Letras Ribeirao Preto, Dept Quim, Av Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP, BrazilOswaldo Cruz Fdn Fiocruz, Aggeu Magalhaes Res Ctr, Dept Immunol, Recife, PE, BrazilUniv Sao Paulo, Dept Med, Fac Med Ribeirao Preto, Av Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP, BrazilUniv Paris 07, Sorbonne Paris Cite, Hop St Louis,Serv Rech Hematoimmunol,IUH, UMR Commissariat Energie Atom & Energies,iMETI, 1 Ave Claude Vellefaux, F-75475 Paris 10, FranceUniv Estadual Paulista, Fac Med Botucatu, Dept Patol, Botucatu, SP, BrazilUniv Estadual Paulista, Fac Med Botucatu, Dept Patol, Botucatu, SP, BrazilCAPES: 653/09CNPq: 309572/2014-2CNPq: 304931/2014-4CNPq: 304471/2013-5CNPq: 406594/2013-9Elsevier B.V.Universidade de São Paulo (USP)Ist Sci San RaffaeleOswaldo Cruz Fdn FiocruzUniversidade Estadual Paulista (Unesp)Albuquerque, Rafael S. deMendes-Junior, Celso TeixeiraLucena-Silva, NormaLopes da Silva, Camila LealRassi, Diane MeireVeiga-Castelli, Luciana C.Foss-Freitas, Maria CristinaFoss, Milton CesarSaloum Deghaide, Neifi HassanMoreau, PhilippeGregori, SilviaCastelli, Erick C. [UNESP]Donadi, Eduardo Antonio2018-11-26T16:32:46Z2018-11-26T16:32:46Z2016-04-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article358-364application/pdfhttp://dx.doi.org/10.1016/j.humimm.2016.02.001Human Immunology. New York: Elsevier Science Inc, v. 77, n. 4, p. 358-364, 2016.0198-8859http://hdl.handle.net/11449/16144410.1016/j.humimm.2016.02.001WOS:000374724000011WOS000374724000011.pdfWeb of Sciencereponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengHuman Immunology0,856info:eu-repo/semantics/openAccess2024-09-03T13:18:34Zoai:repositorio.unesp.br:11449/161444Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestrepositoriounesp@unesp.bropendoar:29462024-09-03T13:18:34Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Association of HLA-G 3 ' untranslated region variants with type 1 diabetes mellitus |
title |
Association of HLA-G 3 ' untranslated region variants with type 1 diabetes mellitus |
spellingShingle |
Association of HLA-G 3 ' untranslated region variants with type 1 diabetes mellitus Albuquerque, Rafael S. de Type 1 diabetes mellitus HLA-G 3 ' untranslated region Gene regulation Brazilians |
title_short |
Association of HLA-G 3 ' untranslated region variants with type 1 diabetes mellitus |
title_full |
Association of HLA-G 3 ' untranslated region variants with type 1 diabetes mellitus |
title_fullStr |
Association of HLA-G 3 ' untranslated region variants with type 1 diabetes mellitus |
title_full_unstemmed |
Association of HLA-G 3 ' untranslated region variants with type 1 diabetes mellitus |
title_sort |
Association of HLA-G 3 ' untranslated region variants with type 1 diabetes mellitus |
author |
Albuquerque, Rafael S. de |
author_facet |
Albuquerque, Rafael S. de Mendes-Junior, Celso Teixeira Lucena-Silva, Norma Lopes da Silva, Camila Leal Rassi, Diane Meire Veiga-Castelli, Luciana C. Foss-Freitas, Maria Cristina Foss, Milton Cesar Saloum Deghaide, Neifi Hassan Moreau, Philippe Gregori, Silvia Castelli, Erick C. [UNESP] Donadi, Eduardo Antonio |
author_role |
author |
author2 |
Mendes-Junior, Celso Teixeira Lucena-Silva, Norma Lopes da Silva, Camila Leal Rassi, Diane Meire Veiga-Castelli, Luciana C. Foss-Freitas, Maria Cristina Foss, Milton Cesar Saloum Deghaide, Neifi Hassan Moreau, Philippe Gregori, Silvia Castelli, Erick C. [UNESP] Donadi, Eduardo Antonio |
author2_role |
author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Ist Sci San Raffaele Oswaldo Cruz Fdn Fiocruz Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Albuquerque, Rafael S. de Mendes-Junior, Celso Teixeira Lucena-Silva, Norma Lopes da Silva, Camila Leal Rassi, Diane Meire Veiga-Castelli, Luciana C. Foss-Freitas, Maria Cristina Foss, Milton Cesar Saloum Deghaide, Neifi Hassan Moreau, Philippe Gregori, Silvia Castelli, Erick C. [UNESP] Donadi, Eduardo Antonio |
dc.subject.por.fl_str_mv |
Type 1 diabetes mellitus HLA-G 3 ' untranslated region Gene regulation Brazilians |
topic |
Type 1 diabetes mellitus HLA-G 3 ' untranslated region Gene regulation Brazilians |
description |
Besides the well recognized association of HLA-DRB1 and DQB1 alleles with type 1 diabetes mellitus (T1D), linkage studies have identified a gene region close to the non-classical class I HLA-G gene as an independent susceptibility marker. HLA-G is constitutively expressed in the endocrine compartment of the human pancreas and may play a role in controlling autoimmune responses. We evaluated the genetic diversity of the 3' untranslated region (3'UTR) of HLA-G, which have been associated with HLA-G mRNA post-transcriptional regulation, in 120 Brazilian T1D patients and in 120 healthy controls. We found the +3001 T allele was observed only in T1D patients. Notably, the +3001 T allele was in linkage disequilibrium with polymorphic sites associated with low production of HLA-G mRNA or soluble HLA-G levels. Moreover, T1D patients showed a low frequency of the HLA-G 3'UTR-17 (14bpINS/+3001T/+3003T/+30 10C/+3027C/+3035T/+3142G/+3187A/+3196C). The +3010 CC genotype and the UTR-3 haplotype (14bp DEL/+3001C/+3003T/+3010C/+3027C/+3035C/+3142G/+3187A/+3196C), associated with low and moderate soluble HLA-G expression, respectively, were underrepresented in patients. The decreased expression of HLA-G at the pancreas level should be detrimental in individuals genetically prone to produce less HLA-G. (C) 2016 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-04-01 2018-11-26T16:32:46Z 2018-11-26T16:32:46Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1016/j.humimm.2016.02.001 Human Immunology. New York: Elsevier Science Inc, v. 77, n. 4, p. 358-364, 2016. 0198-8859 http://hdl.handle.net/11449/161444 10.1016/j.humimm.2016.02.001 WOS:000374724000011 WOS000374724000011.pdf |
url |
http://dx.doi.org/10.1016/j.humimm.2016.02.001 http://hdl.handle.net/11449/161444 |
identifier_str_mv |
Human Immunology. New York: Elsevier Science Inc, v. 77, n. 4, p. 358-364, 2016. 0198-8859 10.1016/j.humimm.2016.02.001 WOS:000374724000011 WOS000374724000011.pdf |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Human Immunology 0,856 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
358-364 application/pdf |
dc.publisher.none.fl_str_mv |
Elsevier B.V. |
publisher.none.fl_str_mv |
Elsevier B.V. |
dc.source.none.fl_str_mv |
Web of Science reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
repositoriounesp@unesp.br |
_version_ |
1810021421183664128 |