Common genetic variation in KATNAL1 non‐coding regions is involved in the susceptibility to severe phenotypes 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/10451/54503 |
Resumo: | © 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
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Common genetic variation in KATNAL1 non‐coding regions is involved in the susceptibility to severe phenotypes of male infertilityKATNAL1SNPMale infertilitySpermatogenesisSplicing© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Background: Previous studies in animal models evidenced that genetic mutations of KATNAL1, resulting in dysfunction of its encoded protein, lead to male infertility through disruption of microtubule remodelling and premature germ cell exfoliation. Subsequent studies in humans also suggested a possible role of KATNAL1 single-nucleotide polymorphisms in the development of male infertility as a consequence of severe spermatogenic failure. Objectives: The main objective of the present study is to evaluate the effect of the common genetic variation of KATNAL1 in a large and phenotypically well-characterised cohort of infertile men because of severe spermatogenic failure. Materials and methods: A total of 715 infertile men because of severe spermatogenic failure, including 210 severe oligospermia and 505 non-obstructive azoospermia patients, as well as 1058 unaffected controls were genotyped for three KATNAL1 single-nucleotide polymorphism taggers (rs2077011, rs7338931 and rs2149971). Case-control association analyses by logistic regression assuming different models and in silico functional characterisation of risk variants were conducted. Results: Genetic associations were observed between the three analysed taggers and different severe spermatogenic failure groups. However, in all cases, the haplotype model (rs2077011*C | rs7338931*T | rs2149971*A) better explained the observed associations than the three risk alleles independently. This haplotype was associated with non-obstructive azoospermia (adjusted p = 4.96E-02, odds ratio = 2.97), Sertoli-cell only syndrome (adjusted p = 2.83E-02, odds ratio = 5.16) and testicular sperm extraction unsuccessful outcomes (adjusted p = 8.99E-04, odds ratio = 6.13). The in silico analyses indicated that the effect on severe spermatogenic failure predisposition could be because of an alteration of the KATNAL1 splicing pattern. Conclusions: Specific allelic combinations of KATNAL1 genetic polymorphisms may confer a risk of developing severe male infertility phenotypes by favouring the overrepresentation of a short non-functional transcript isoform in the testis.This work was supported by the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (refs. SAF2016-78722-R and PID2020-120157RB-I00), the ‘Instituto de Salud Carlos III’ (Fondo de Investigaciones Sanitarias)/Fondo Europeo de Desarrollo Regional ‘Una manera de hacer Europa’ (FIS/FEDER) (ref. DTS18/00101 to Sara Larriba), the Generalitat de Catalunya (ref. 2017SGR191), the ‘Ramón y Cajal’ program (ref. RYC-2014-16458) and the ‘Juan de la Cierva Incorporación’ program (ref. IJC2018-038026-I), as well as the Andalusian Government through the R&D&i Projects Grants for Universities and Public Research Entities (ref. PY20_00212), which include FEDER funds. Andrea Guzmán-Jiménez was a recipient of a grant from the Spanish Ministry of Education and Professional Training (‘Becas de Colaboración en Departamentos Universitarios para el curso académico 2020/2021’). Patricia I. Marques is supported by the FCT post-doctoral fellowship (SFRH/BPD/120777/2016), financed from the Portuguese State Budget of the Ministry for Science, Technology and High Education and from the European Social Fund, available through the ‘Programa Operacional do Capital Humano’. João Gonçalves was partially funded by FCT/MCTES through national funds attributed to the Centre for Toxicogenomics and Human Health—ToxOmics (UID/BIM/00009/2016 and UIDB/00009/2020). Sara Larriba is sponsored by the Researchers Consolidation Program (ISCIII SNS/Dpt. Salut Generalitat de Catalunya) (CES09/020).WileyRepositório da Universidade de LisboaCerván‐Martín, MiriamBossini‐Castillo, LaraGuzmán‐Jiménez, AndreaRivera‐Egea, RocíoGarrido, NicolásLujan, SaturninoRomeu, GemaSantos-Ribeiro, SamuelCastilla, José AntonioGonzalvo, María del CarmenClavero, AnaMaldonado, VicenteVicente, Francisco JavierBurgos, MiguelJiménez, RafaelGonzález‐Muñoz, SaraSánchez‐Curbelo, JosvanyLópez‐Rodrigo, OlgaPereira‐Caetano, IrisMarques, Patricia IsabelCarvalho, FilipaBarros, AlbertoBassas, LluísSeixas, SusanaGonçalves, JoãoLarriba, SaraLopes, Alexandra ManuelPalomino‐Morales, Rogelio JesúsCarmona, Francisco David2022-09-19T14:56:27Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/54503engAndrology. 2022 Oct;10(7):1339-13502047-291910.1111/andr.132212047-2927info: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:RCAAP2024-11-20T18:16:42Zoai:repositorio.ul.pt:10451/54503Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-11-20T18:16:42Repositório 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 |
Common genetic variation in KATNAL1 non‐coding regions is involved in the susceptibility to severe phenotypes of male infertility |
| title |
Common genetic variation in KATNAL1 non‐coding regions is involved in the susceptibility to severe phenotypes of male infertility |
| spellingShingle |
Common genetic variation in KATNAL1 non‐coding regions is involved in the susceptibility to severe phenotypes of male infertility Cerván‐Martín, Miriam KATNAL1 SNP Male infertility Spermatogenesis Splicing |
| title_short |
Common genetic variation in KATNAL1 non‐coding regions is involved in the susceptibility to severe phenotypes of male infertility |
| title_full |
Common genetic variation in KATNAL1 non‐coding regions is involved in the susceptibility to severe phenotypes of male infertility |
| title_fullStr |
Common genetic variation in KATNAL1 non‐coding regions is involved in the susceptibility to severe phenotypes of male infertility |
| title_full_unstemmed |
Common genetic variation in KATNAL1 non‐coding regions is involved in the susceptibility to severe phenotypes of male infertility |
| title_sort |
Common genetic variation in KATNAL1 non‐coding regions is involved in the susceptibility to severe phenotypes of male infertility |
| author |
Cerván‐Martín, Miriam |
| author_facet |
Cerván‐Martín, Miriam Bossini‐Castillo, Lara Guzmán‐Jiménez, Andrea Rivera‐Egea, Rocío Garrido, Nicolás Lujan, Saturnino Romeu, Gema Santos-Ribeiro, Samuel Castilla, José Antonio Gonzalvo, María del Carmen Clavero, Ana Maldonado, Vicente Vicente, Francisco Javier Burgos, Miguel Jiménez, Rafael González‐Muñoz, Sara Sánchez‐Curbelo, Josvany López‐Rodrigo, Olga Pereira‐Caetano, Iris Marques, Patricia Isabel Carvalho, Filipa Barros, Alberto Bassas, Lluís Seixas, Susana Gonçalves, João Larriba, Sara Lopes, Alexandra Manuel Palomino‐Morales, Rogelio Jesús Carmona, Francisco David |
| author_role |
author |
| author2 |
Bossini‐Castillo, Lara Guzmán‐Jiménez, Andrea Rivera‐Egea, Rocío Garrido, Nicolás Lujan, Saturnino Romeu, Gema Santos-Ribeiro, Samuel Castilla, José Antonio Gonzalvo, María del Carmen Clavero, Ana Maldonado, Vicente Vicente, Francisco Javier Burgos, Miguel Jiménez, Rafael González‐Muñoz, Sara Sánchez‐Curbelo, Josvany López‐Rodrigo, Olga Pereira‐Caetano, Iris Marques, Patricia Isabel Carvalho, Filipa Barros, Alberto Bassas, Lluís Seixas, Susana Gonçalves, João Larriba, Sara Lopes, Alexandra Manuel Palomino‐Morales, Rogelio Jesús Carmona, Francisco David |
| 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 |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Cerván‐Martín, Miriam Bossini‐Castillo, Lara Guzmán‐Jiménez, Andrea Rivera‐Egea, Rocío Garrido, Nicolás Lujan, Saturnino Romeu, Gema Santos-Ribeiro, Samuel Castilla, José Antonio Gonzalvo, María del Carmen Clavero, Ana Maldonado, Vicente Vicente, Francisco Javier Burgos, Miguel Jiménez, Rafael González‐Muñoz, Sara Sánchez‐Curbelo, Josvany López‐Rodrigo, Olga Pereira‐Caetano, Iris Marques, Patricia Isabel Carvalho, Filipa Barros, Alberto Bassas, Lluís Seixas, Susana Gonçalves, João Larriba, Sara Lopes, Alexandra Manuel Palomino‐Morales, Rogelio Jesús Carmona, Francisco David |
| dc.subject.por.fl_str_mv |
KATNAL1 SNP Male infertility Spermatogenesis Splicing |
| topic |
KATNAL1 SNP Male infertility Spermatogenesis Splicing |
| description |
© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
| publishDate |
2022 |
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2022-09-19T14:56:27Z 2022 2022-01-01T00:00:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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http://hdl.handle.net/10451/54503 |
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http://hdl.handle.net/10451/54503 |
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eng |
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eng |
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Andrology. 2022 Oct;10(7):1339-1350 2047-2919 10.1111/andr.13221 2047-2927 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Wiley |
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Wiley |
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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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RCAAP |
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RCAAP |
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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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