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Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility
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 wer...
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Formato: | Online Artículo Texto |
| Lenguaje: | English |
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Nature Publishing Group UK
2022
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| Materias: | |
| Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9649734/ https://www.ncbi.nlm.nih.gov/pubmed/36357561 http://dx.doi.org/10.1038/s42003-022-04192-0 |
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| author | Cerván-Martín, Miriam Tüttelmann, Frank Lopes, Alexandra M. Bossini-Castillo, Lara Rivera-Egea, Rocío Garrido, Nicolás Lujan, Saturnino Romeu, Gema Santos-Ribeiro, Samuel Castilla, José A. Carmen Gonzalvo, M. Clavero, Ana Maldonado, Vicente Vicente, F. Javier González-Muñoz, Sara Guzmán-Jiménez, Andrea Burgos, Miguel Jiménez, Rafael Pacheco, Alberto González, Cristina Gómez, Susana Amorós, David Aguilar, Jesus Quintana, Fernando Calhaz-Jorge, Carlos Aguiar, Ana Nunes, Joaquim Sousa, Sandra Pereira, Isabel Pinto, Maria Graça Correia, Sónia Sánchez-Curbelo, Josvany López-Rodrigo, Olga Martín, Javier Pereira-Caetano, Iris Marques, Patricia I. Carvalho, Filipa Barros, Alberto Gromoll, Jörg Bassas, Lluís Seixas, Susana Gonçalves, João Larriba, Sara Kliesch, Sabine Palomino-Morales, Rogelio J. Carmona, F. David |
| author_facet | Cerván-Martín, Miriam Tüttelmann, Frank Lopes, Alexandra M. Bossini-Castillo, Lara Rivera-Egea, Rocío Garrido, Nicolás Lujan, Saturnino Romeu, Gema Santos-Ribeiro, Samuel Castilla, José A. Carmen Gonzalvo, M. Clavero, Ana Maldonado, Vicente Vicente, F. Javier González-Muñoz, Sara Guzmán-Jiménez, Andrea Burgos, Miguel Jiménez, Rafael Pacheco, Alberto González, Cristina Gómez, Susana Amorós, David Aguilar, Jesus Quintana, Fernando Calhaz-Jorge, Carlos Aguiar, Ana Nunes, Joaquim Sousa, Sandra Pereira, Isabel Pinto, Maria Graça Correia, Sónia Sánchez-Curbelo, Josvany López-Rodrigo, Olga Martín, Javier Pereira-Caetano, Iris Marques, Patricia I. Carvalho, Filipa Barros, Alberto Gromoll, Jörg Bassas, Lluís Seixas, Susana Gonçalves, João Larriba, Sara Kliesch, Sabine Palomino-Morales, Rogelio J. Carmona, F. David |
| author_sort | Cerván-Martín, Miriam |
| collection | PubMed |
| 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. |
| format | Online Article Text |
| id | pubmed-9649734 |
| institution | National Center for Biotechnology Information |
| language | English |
| publishDate | 2022 |
| publisher | Nature Publishing Group UK |
| record_format | MEDLINE/PubMed |
| spelling | pubmed-96497342022-11-15 Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility Cerván-Martín, Miriam Tüttelmann, Frank Lopes, Alexandra M. Bossini-Castillo, Lara Rivera-Egea, Rocío Garrido, Nicolás Lujan, Saturnino Romeu, Gema Santos-Ribeiro, Samuel Castilla, José A. Carmen Gonzalvo, M. Clavero, Ana Maldonado, Vicente Vicente, F. Javier González-Muñoz, Sara Guzmán-Jiménez, Andrea Burgos, Miguel Jiménez, Rafael Pacheco, Alberto González, Cristina Gómez, Susana Amorós, David Aguilar, Jesus Quintana, Fernando Calhaz-Jorge, Carlos Aguiar, Ana Nunes, Joaquim Sousa, Sandra Pereira, Isabel Pinto, Maria Graça Correia, Sónia Sánchez-Curbelo, Josvany López-Rodrigo, Olga Martín, Javier Pereira-Caetano, Iris Marques, Patricia I. Carvalho, Filipa Barros, Alberto Gromoll, Jörg Bassas, Lluís Seixas, Susana Gonçalves, João Larriba, Sara Kliesch, Sabine Palomino-Morales, Rogelio J. Carmona, F. David Commun Biol Article 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. Nature Publishing Group UK 2022-11-10 /pmc/articles/PMC9649734/ /pubmed/36357561 http://dx.doi.org/10.1038/s42003-022-04192-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
| spellingShingle | Article Cerván-Martín, Miriam Tüttelmann, Frank Lopes, Alexandra M. Bossini-Castillo, Lara Rivera-Egea, Rocío Garrido, Nicolás Lujan, Saturnino Romeu, Gema Santos-Ribeiro, Samuel Castilla, José A. Carmen Gonzalvo, M. Clavero, Ana Maldonado, Vicente Vicente, F. Javier González-Muñoz, Sara Guzmán-Jiménez, Andrea Burgos, Miguel Jiménez, Rafael Pacheco, Alberto González, Cristina Gómez, Susana Amorós, David Aguilar, Jesus Quintana, Fernando Calhaz-Jorge, Carlos Aguiar, Ana Nunes, Joaquim Sousa, Sandra Pereira, Isabel Pinto, Maria Graça Correia, Sónia Sánchez-Curbelo, Josvany López-Rodrigo, Olga Martín, Javier Pereira-Caetano, Iris Marques, Patricia I. Carvalho, Filipa Barros, Alberto Gromoll, Jörg Bassas, Lluís Seixas, Susana Gonçalves, João Larriba, Sara Kliesch, Sabine Palomino-Morales, Rogelio J. Carmona, F. David 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 |
| 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_short | 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 |
| topic | Article |
| url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9649734/ https://www.ncbi.nlm.nih.gov/pubmed/36357561 http://dx.doi.org/10.1038/s42003-022-04192-0 |
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