The rare DRB1*04:08-DQ8 haplotype is the main HLA class II genetic driver and discriminative factor of Early-onset Type 1 diabetes in the Portuguese population

Detalhes bibliográficos
Autor(a) principal: Caramalho, Iris
Data de Publicação: 2023
Outros Autores: Matoso, Paula, Ligeiro, Dário, Paixão, Tiago, Sobral, Daniel, Fitas, Ana Laura, Limbert, Catarina, Demengeot, Jocelyne, Penha-Gonçalves, Carlos
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/162725
Resumo: Funding Information: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the European Foundation for the Study of Diabetes (EFSD/JDRF/Lilly Programme 2016), Maratona da Saúde and Fundação para a Ciência e a Tecnologia (CEECIND/00148/2017 to Iris Caramalho). Acknowledgments Publisher Copyright: Copyright © 2024 Caramalho, Matoso, Ligeiro, Paixão, Sobral, Fitas, Limbert, Demengeot and Penha-Gonçalves.
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spelling The rare DRB1*04:08-DQ8 haplotype is the main HLA class II genetic driver and discriminative factor of Early-onset Type 1 diabetes in the Portuguese populationage of onsetEarly-onset Type 1 diabetesHLA class IIT1D endotypesType 1 diabetesImmunology and AllergyImmunologySDG 3 - Good Health and Well-beingFunding Information: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the European Foundation for the Study of Diabetes (EFSD/JDRF/Lilly Programme 2016), Maratona da Saúde and Fundação para a Ciência e a Tecnologia (CEECIND/00148/2017 to Iris Caramalho). Acknowledgments Publisher Copyright: Copyright © 2024 Caramalho, Matoso, Ligeiro, Paixão, Sobral, Fitas, Limbert, Demengeot and Penha-Gonçalves.Introduction: Early-onset Type 1 diabetes (EOT1D) is considered a disease subtype with distinctive immunological and clinical features. While both Human Leukocyte Antigen (HLA) and non-HLA variants contribute to age at T1D diagnosis, detailed analyses of EOT1D-specific genetic determinants are still lacking. This study scrutinized the involvement of the HLA class II locus in EOT1D genetic control. Methods: We conducted genetic association and regularized logistic regression analyses to evaluate genotypic, haplotypic and allelic variants in DRB1, DQA1 and DQB1 genes in children with EOT1D (diagnosed at £5 years of age; n=97), individuals with later-onset disease (LaOT1D; diagnosed 8-30 years of age; n=96) and nondiabetic control subjects (n=169), in the Portuguese population. Results: Allelic association analysis of EOT1D and LaOT1D unrelated patients in comparison with controls, revealed that the rare DRB1*04:08 allele is a distinctive EOT1D susceptibility factor (corrected p-value=7.0x10-7). Conversely, the classical T1D risk allele DRB1*04:05 was absent in EOT1D children while was associated with LaOT1D (corrected p-value=1.4x10-2). In corroboration, HLA class II haplotype analysis showed that the rare DRB1*04:08-DQ8 haplotype is specifically associated with EOT1D (corrected p-value=1.4x10-5) and represents the major HLA class II genetic driver and discriminative factor in the development of early onset disease. Discussion: This study uncovered that EOT1D holds a distinctive spectrum of HLA class II susceptibility loci, which includes risk factors overlapping with LaOT1D and discriminative genetic configurations. These findings warrant replication studies in larger multicentric settings encompassing other ethnicities and may impact target screening strategies and follow-up of young children with high T1D genetic risk as well as personalized therapeutic approaches.Comprehensive Health Research Centre (CHRC) - pólo NMSNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNCaramalho, IrisMatoso, PaulaLigeiro, DárioPaixão, TiagoSobral, DanielFitas, Ana LauraLimbert, CatarinaDemengeot, JocelynePenha-Gonçalves, Carlos2024-01-24T17:11:11Z20232023-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10362/162725eng1664-3224PURE: 82231917https://doi.org/10.3389/fimmu.2023.1299609info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:45:42Zoai:run.unl.pt:10362/162725Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:59:03.000819Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv The rare DRB1*04:08-DQ8 haplotype is the main HLA class II genetic driver and discriminative factor of Early-onset Type 1 diabetes in the Portuguese population
title The rare DRB1*04:08-DQ8 haplotype is the main HLA class II genetic driver and discriminative factor of Early-onset Type 1 diabetes in the Portuguese population
spellingShingle The rare DRB1*04:08-DQ8 haplotype is the main HLA class II genetic driver and discriminative factor of Early-onset Type 1 diabetes in the Portuguese population
Caramalho, Iris
age of onset
Early-onset Type 1 diabetes
HLA class II
T1D endotypes
Type 1 diabetes
Immunology and Allergy
Immunology
SDG 3 - Good Health and Well-being
title_short The rare DRB1*04:08-DQ8 haplotype is the main HLA class II genetic driver and discriminative factor of Early-onset Type 1 diabetes in the Portuguese population
title_full The rare DRB1*04:08-DQ8 haplotype is the main HLA class II genetic driver and discriminative factor of Early-onset Type 1 diabetes in the Portuguese population
title_fullStr The rare DRB1*04:08-DQ8 haplotype is the main HLA class II genetic driver and discriminative factor of Early-onset Type 1 diabetes in the Portuguese population
title_full_unstemmed The rare DRB1*04:08-DQ8 haplotype is the main HLA class II genetic driver and discriminative factor of Early-onset Type 1 diabetes in the Portuguese population
title_sort The rare DRB1*04:08-DQ8 haplotype is the main HLA class II genetic driver and discriminative factor of Early-onset Type 1 diabetes in the Portuguese population
author Caramalho, Iris
author_facet Caramalho, Iris
Matoso, Paula
Ligeiro, Dário
Paixão, Tiago
Sobral, Daniel
Fitas, Ana Laura
Limbert, Catarina
Demengeot, Jocelyne
Penha-Gonçalves, Carlos
author_role author
author2 Matoso, Paula
Ligeiro, Dário
Paixão, Tiago
Sobral, Daniel
Fitas, Ana Laura
Limbert, Catarina
Demengeot, Jocelyne
Penha-Gonçalves, Carlos
author2_role author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Comprehensive Health Research Centre (CHRC) - pólo NMS
NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
RUN
dc.contributor.author.fl_str_mv Caramalho, Iris
Matoso, Paula
Ligeiro, Dário
Paixão, Tiago
Sobral, Daniel
Fitas, Ana Laura
Limbert, Catarina
Demengeot, Jocelyne
Penha-Gonçalves, Carlos
dc.subject.por.fl_str_mv age of onset
Early-onset Type 1 diabetes
HLA class II
T1D endotypes
Type 1 diabetes
Immunology and Allergy
Immunology
SDG 3 - Good Health and Well-being
topic age of onset
Early-onset Type 1 diabetes
HLA class II
T1D endotypes
Type 1 diabetes
Immunology and Allergy
Immunology
SDG 3 - Good Health and Well-being
description Funding Information: The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the European Foundation for the Study of Diabetes (EFSD/JDRF/Lilly Programme 2016), Maratona da Saúde and Fundação para a Ciência e a Tecnologia (CEECIND/00148/2017 to Iris Caramalho). Acknowledgments Publisher Copyright: Copyright © 2024 Caramalho, Matoso, Ligeiro, Paixão, Sobral, Fitas, Limbert, Demengeot and Penha-Gonçalves.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023-01-01T00:00:00Z
2024-01-24T17:11:11Z
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://hdl.handle.net/10362/162725
url http://hdl.handle.net/10362/162725
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1664-3224
PURE: 82231917
https://doi.org/10.3389/fimmu.2023.1299609
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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