Effect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohort
| Autor(a) principal: | |
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| Data de Publicação: | 2021 |
| 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/10400.18/7922 |
Resumo: | IVIRMA Group, Lisbon Clinical Group: Alberto Pacheco, Cristina González, Susana Gómez, David Amorós, Jesus Aguilar, Fernando Quintana, Carlos Calhaz-Jorge, Ana Aguiar, Joaquim Nunes, Sandra Sousa, Maria Graça Pinto, Sónia Correia |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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7160 |
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Effect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohortSpermatogenesisMale InfertilityAzoospermiaSevere OligozoospermiaNon-obstructive AzoospermiaDoenças GenéticasIVIRMA Group, Lisbon Clinical Group: Alberto Pacheco, Cristina González, Susana Gómez, David Amorós, Jesus Aguilar, Fernando Quintana, Carlos Calhaz-Jorge, Ana Aguiar, Joaquim Nunes, Sandra Sousa, Maria Graça Pinto, Sónia CorreiaBackground: Severe spermatogenic failure (SpF) represents the most extreme manifestation of male infertility, as it decreases drastically the semen quality leading to either severe oligospermia (SO, <5 million spermatozoa/mL semen) or non-obstructive azoospermia (NOA, complete lack of spermatozoa in the ejaculate without obstructive causes). Objectives: The main objective of the present study is to analyze in the Iberian population the effect of 6 single-nucleotide polymorphisms (SNPs) previously associated with NOA in Han Chinese through genome-wide association studies (GWAS) and to establish their possible functional relevance in the development of specific SpF patterns. Materials and methods: We genotyped 674 Iberian infertile men (including 480 NOA and 194 SO patients) and 1058 matched unaffected controls for the GWAS-associated variants PRMT6-rs12097821, PEX10-rs2477686, CDC42BPA-rs3000811, IL17A-rs13206743, ABLIM1-rs7099208, and SOX5-rs10842262. Their association with SpF, SO, NOA, and different NOA phenotypes was evaluated by logistic regression models, and their functional relevance was defined by comprehensive interrogation of public resources. Results: ABLIM1-rs7099208 was associated with SpF under both additive (OR = 0.86, p = 0.036) and dominant models (OR = 0.78, p = 0.026). The CDC42BPA-rs3000811 minor allele frequency was significantly increased in the subgroup of NOA patients showing maturation arrest (MA) of germ cells compared to the remaining NOA cases under the recessive model (OR = 4.45, p = 0.044). The PEX10-rs2477686 SNP was associated with a negative testicular sperm extraction (TESE) outcome under the additive model (OR = 1.32, p = 0.034). The analysis of functional annotations suggested that these variants affect the testis-specific expression of nearby genes and that lincRNA may play a role in SpF. Conclusions: Our data support the association of three previously reported NOA risk variants in Asians (ABLIM1-rs7099208, CDC42BPA-rs3000811, and PEX10-rs2477686) with different manifestations of SpF in Iberians of European descent, likely by influencing gene expression and lincRNA deregulation.Wiley/ American Society of Andrology and European Academy of AndrologyRepositório Científico do Instituto Nacional de SaúdeCerván‐Martín, MiriamBossini‐Castillo, LaraRivera‐Egea, RocíoGarrido, NicolásLuján, SaturninoRomeu, GemaSantos‐Ribeiro, SamuelIVIRMA Group, Lisbon Clinical GroupCastilla, José A.Gonzalvo, María del CarmenClavero, AnaVicente, Francisco JavierGuzmán‐Jiménez, AndreaBurgos, MiguelBarrionuevo, Francisco JavierJiménez, RafaelSánchez‐Curbelo, JosvanyLópez‐Rodrigo, OlgaPeraza, María FernandaPereira‐Caetano, IrisMarques, Patrícia IsabelCarvalho, FilipaBarros, AlbertoBassas, LuísSeixas, SusanaGonçalves, JoãoLarriba, SaraLopes, Alexandra ManuelCarmona, Francisco DavidPalomino‐Morales, Rogelio Jesús2022-02-03T16:43:45Z2021-072021-07-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10400.18/7922engAndrology. 2021 Jul;9(4):1151-1165. doi: 10.1111/andr.13009. Epub 2021 Apr 20.2047-291910.1111/andr.13009info:eu-repo/semantics/embargoedAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-20T15:42:17Zoai:repositorio.insa.pt:10400.18/7922Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T18:42:34.488143Repositório 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 |
Effect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohort |
| title |
Effect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohort |
| spellingShingle |
Effect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohort Cerván‐Martín, Miriam Spermatogenesis Male Infertility Azoospermia Severe Oligozoospermia Non-obstructive Azoospermia Doenças Genéticas |
| title_short |
Effect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohort |
| title_full |
Effect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohort |
| title_fullStr |
Effect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohort |
| title_full_unstemmed |
Effect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohort |
| title_sort |
Effect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohort |
| author |
Cerván‐Martín, Miriam |
| author_facet |
Cerván‐Martín, Miriam Bossini‐Castillo, Lara Rivera‐Egea, Rocío Garrido, Nicolás Luján, Saturnino Romeu, Gema Santos‐Ribeiro, Samuel IVIRMA Group, Lisbon Clinical Group Castilla, José A. Gonzalvo, María del Carmen Clavero, Ana Vicente, Francisco Javier Guzmán‐Jiménez, Andrea Burgos, Miguel Barrionuevo, Francisco Javier Jiménez, Rafael Sánchez‐Curbelo, Josvany López‐Rodrigo, Olga Peraza, María Fernanda Pereira‐Caetano, Iris Marques, Patrícia Isabel Carvalho, Filipa Barros, Alberto Bassas, Luís Seixas, Susana Gonçalves, João Larriba, Sara Lopes, Alexandra Manuel Carmona, Francisco David Palomino‐Morales, Rogelio Jesús |
| author_role |
author |
| author2 |
Bossini‐Castillo, Lara Rivera‐Egea, Rocío Garrido, Nicolás Luján, Saturnino Romeu, Gema Santos‐Ribeiro, Samuel IVIRMA Group, Lisbon Clinical Group Castilla, José A. Gonzalvo, María del Carmen Clavero, Ana Vicente, Francisco Javier Guzmán‐Jiménez, Andrea Burgos, Miguel Barrionuevo, Francisco Javier Jiménez, Rafael Sánchez‐Curbelo, Josvany López‐Rodrigo, Olga Peraza, María Fernanda Pereira‐Caetano, Iris Marques, Patrícia Isabel Carvalho, Filipa Barros, Alberto Bassas, Luís Seixas, Susana Gonçalves, João Larriba, Sara Lopes, Alexandra Manuel Carmona, Francisco David Palomino‐Morales, Rogelio Jesús |
| 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 |
| dc.contributor.none.fl_str_mv |
Repositório Científico do Instituto Nacional de Saúde |
| dc.contributor.author.fl_str_mv |
Cerván‐Martín, Miriam Bossini‐Castillo, Lara Rivera‐Egea, Rocío Garrido, Nicolás Luján, Saturnino Romeu, Gema Santos‐Ribeiro, Samuel IVIRMA Group, Lisbon Clinical Group Castilla, José A. Gonzalvo, María del Carmen Clavero, Ana Vicente, Francisco Javier Guzmán‐Jiménez, Andrea Burgos, Miguel Barrionuevo, Francisco Javier Jiménez, Rafael Sánchez‐Curbelo, Josvany López‐Rodrigo, Olga Peraza, María Fernanda Pereira‐Caetano, Iris Marques, Patrícia Isabel Carvalho, Filipa Barros, Alberto Bassas, Luís Seixas, Susana Gonçalves, João Larriba, Sara Lopes, Alexandra Manuel Carmona, Francisco David Palomino‐Morales, Rogelio Jesús |
| dc.subject.por.fl_str_mv |
Spermatogenesis Male Infertility Azoospermia Severe Oligozoospermia Non-obstructive Azoospermia Doenças Genéticas |
| topic |
Spermatogenesis Male Infertility Azoospermia Severe Oligozoospermia Non-obstructive Azoospermia Doenças Genéticas |
| description |
IVIRMA Group, Lisbon Clinical Group: Alberto Pacheco, Cristina González, Susana Gómez, David Amorós, Jesus Aguilar, Fernando Quintana, Carlos Calhaz-Jorge, Ana Aguiar, Joaquim Nunes, Sandra Sousa, Maria Graça Pinto, Sónia Correia |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021-07 2021-07-01T00:00:00Z 2022-02-03T16:43:45Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10400.18/7922 |
| url |
http://hdl.handle.net/10400.18/7922 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Andrology. 2021 Jul;9(4):1151-1165. doi: 10.1111/andr.13009. Epub 2021 Apr 20. 2047-2919 10.1111/andr.13009 |
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info:eu-repo/semantics/embargoedAccess |
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embargoedAccess |
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application/pdf |
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Wiley/ American Society of Andrology and European Academy of Andrology |
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Wiley/ American Society of Andrology and European Academy of Andrology |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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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) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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