Immune and Spermatogenesis-Related Loci are Involved in the Development of Extreme Patterns of Male Infertility
Autor(a) principal: | |
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Data de Publicação: | 2022 |
Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10400.17/4476 |
Resumo: | We conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pattern of SPGF, defined by Sertoli cell-only (SCO) phenotype, namely the MHC class II gene HLA-DRB1 (rs1136759, P = 1.32E-08, OR = 1.80) and an upstream locus of VRK1 (rs115054029, P = 4.24E-08, OR = 3.14), which encodes a protein kinase involved in the regulation of spermatogenesis. The SCO-associated rs1136759 allele (G) determines a serine in the position 13 of the HLA-DRβ1 molecule located in the antigen-binding pocket. Overall, our data support the notion of unexplained SPGF as a complex trait influenced by common variation in the genome, with the SCO phenotype likely representing an immune-mediated condition. |
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Immune and Spermatogenesis-Related Loci are Involved in the Development of Extreme Patterns of Male InfertilityAllelesGenome-Wide Association Study*HumansInfertility, Male* / geneticsInfertility, Male* / geneticsMaleProtein Serine-Threonine KinasesSertoli Cells / metabolismSpermatogenesis / geneticsMAC GINWe conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pattern of SPGF, defined by Sertoli cell-only (SCO) phenotype, namely the MHC class II gene HLA-DRB1 (rs1136759, P = 1.32E-08, OR = 1.80) and an upstream locus of VRK1 (rs115054029, P = 4.24E-08, OR = 3.14), which encodes a protein kinase involved in the regulation of spermatogenesis. The SCO-associated rs1136759 allele (G) determines a serine in the position 13 of the HLA-DRβ1 molecule located in the antigen-binding pocket. Overall, our data support the notion of unexplained SPGF as a complex trait influenced by common variation in the genome, with the SCO phenotype likely representing an immune-mediated condition.Nature Publishing GroupRepositório do Centro Hospitalar Universitário de Lisboa Central, EPECerván-Martín, MTüttelmann, FLopes, AMBossini-Castillo, LRivera-Egea, RGarrido, NLujan, SRomeu, GSantos-Ribeiro, SCastilla, JACarmen Gonzalvo, MClavero, AMaldonado, VVicente, FJGonzález-Muñoz, SGuzmán-Jiménez, ABurgos, MJiménez, RPacheco, AGonzález, CGómez, SAmorós, DAguilar, JQuintana, FCalhaz-Jorge, CAguiar, ANunes, JSousa, SPereira, IPinto, MGCorreia, SSánchez-Curbelo, JLópez-Rodrigo, OMartín, JPereira-Caetano, IMarques, PICarvalho, FBarros, AGromoll, JBassas, LSeixas, SGonçalves, JLarriba, SKliesch, SPalomino-Morales, RJCarmona, FD2023-04-12T12:28:02Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.17/4476engCommun Biol . 2022 Nov 10;5(1):122010.1038/s42003-022-04192-0info: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:RCAAP2023-04-16T05:45:30Zoai:repositorio.chlc.min-saude.pt:10400.17/4476Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T17:49:35.820408Repositório 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 |
Immune and Spermatogenesis-Related Loci are Involved in the Development of Extreme Patterns of Male Infertility |
title |
Immune and Spermatogenesis-Related Loci are Involved in the Development of Extreme Patterns of Male Infertility |
spellingShingle |
Immune and Spermatogenesis-Related Loci are Involved in the Development of Extreme Patterns of Male Infertility Cerván-Martín, M Alleles Genome-Wide Association Study* Humans Infertility, Male* / genetics Infertility, Male* / genetics Male Protein Serine-Threonine Kinases Sertoli Cells / metabolism Spermatogenesis / genetics MAC GIN |
title_short |
Immune and Spermatogenesis-Related Loci are Involved in the Development of Extreme Patterns of Male Infertility |
title_full |
Immune and Spermatogenesis-Related Loci are Involved in the Development of Extreme Patterns of Male Infertility |
title_fullStr |
Immune and Spermatogenesis-Related Loci are Involved in the Development of Extreme Patterns of Male Infertility |
title_full_unstemmed |
Immune and Spermatogenesis-Related Loci are Involved in the Development of Extreme Patterns of Male Infertility |
title_sort |
Immune and Spermatogenesis-Related Loci are Involved in the Development of Extreme Patterns of Male Infertility |
author |
Cerván-Martín, M |
author_facet |
Cerván-Martín, M Tüttelmann, F Lopes, AM Bossini-Castillo, L Rivera-Egea, R Garrido, N Lujan, S Romeu, G Santos-Ribeiro, S Castilla, JA Carmen Gonzalvo, M Clavero, A Maldonado, V Vicente, FJ González-Muñoz, S Guzmán-Jiménez, A Burgos, M Jiménez, R Pacheco, A González, C Gómez, S Amorós, D Aguilar, J Quintana, F Calhaz-Jorge, C Aguiar, A Nunes, J Sousa, S Pereira, I Pinto, MG Correia, S Sánchez-Curbelo, J López-Rodrigo, O Martín, J Pereira-Caetano, I Marques, PI Carvalho, F Barros, A Gromoll, J Bassas, L Seixas, S Gonçalves, J Larriba, S Kliesch, S Palomino-Morales, RJ Carmona, FD |
author_role |
author |
author2 |
Tüttelmann, F Lopes, AM Bossini-Castillo, L Rivera-Egea, R Garrido, N Lujan, S Romeu, G Santos-Ribeiro, S Castilla, JA Carmen Gonzalvo, M Clavero, A Maldonado, V Vicente, FJ González-Muñoz, S Guzmán-Jiménez, A Burgos, M Jiménez, R Pacheco, A González, C Gómez, S Amorós, D Aguilar, J Quintana, F Calhaz-Jorge, C Aguiar, A Nunes, J Sousa, S Pereira, I Pinto, MG Correia, S Sánchez-Curbelo, J López-Rodrigo, O Martín, J Pereira-Caetano, I Marques, PI Carvalho, F Barros, A Gromoll, J Bassas, L Seixas, S Gonçalves, J Larriba, S Kliesch, S Palomino-Morales, RJ Carmona, FD |
author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
dc.contributor.none.fl_str_mv |
Repositório do Centro Hospitalar Universitário de Lisboa Central, EPE |
dc.contributor.author.fl_str_mv |
Cerván-Martín, M Tüttelmann, F Lopes, AM Bossini-Castillo, L Rivera-Egea, R Garrido, N Lujan, S Romeu, G Santos-Ribeiro, S Castilla, JA Carmen Gonzalvo, M Clavero, A Maldonado, V Vicente, FJ González-Muñoz, S Guzmán-Jiménez, A Burgos, M Jiménez, R Pacheco, A González, C Gómez, S Amorós, D Aguilar, J Quintana, F Calhaz-Jorge, C Aguiar, A Nunes, J Sousa, S Pereira, I Pinto, MG Correia, S Sánchez-Curbelo, J López-Rodrigo, O Martín, J Pereira-Caetano, I Marques, PI Carvalho, F Barros, A Gromoll, J Bassas, L Seixas, S Gonçalves, J Larriba, S Kliesch, S Palomino-Morales, RJ Carmona, FD |
dc.subject.por.fl_str_mv |
Alleles Genome-Wide Association Study* Humans Infertility, Male* / genetics Infertility, Male* / genetics Male Protein Serine-Threonine Kinases Sertoli Cells / metabolism Spermatogenesis / genetics MAC GIN |
topic |
Alleles Genome-Wide Association Study* Humans Infertility, Male* / genetics Infertility, Male* / genetics Male Protein Serine-Threonine Kinases Sertoli Cells / metabolism Spermatogenesis / genetics MAC GIN |
description |
We conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pattern of SPGF, defined by Sertoli cell-only (SCO) phenotype, namely the MHC class II gene HLA-DRB1 (rs1136759, P = 1.32E-08, OR = 1.80) and an upstream locus of VRK1 (rs115054029, P = 4.24E-08, OR = 3.14), which encodes a protein kinase involved in the regulation of spermatogenesis. The SCO-associated rs1136759 allele (G) determines a serine in the position 13 of the HLA-DRβ1 molecule located in the antigen-binding pocket. Overall, our data support the notion of unexplained SPGF as a complex trait influenced by common variation in the genome, with the SCO phenotype likely representing an immune-mediated condition. |
publishDate |
2022 |
dc.date.none.fl_str_mv |
2022 2022-01-01T00:00:00Z 2023-04-12T12:28:02Z |
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/10400.17/4476 |
url |
http://hdl.handle.net/10400.17/4476 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Commun Biol . 2022 Nov 10;5(1):1220 10.1038/s42003-022-04192-0 |
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.publisher.none.fl_str_mv |
Nature Publishing Group |
publisher.none.fl_str_mv |
Nature Publishing Group |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799131576316985344 |