Common genetic variation in KATNAL1 non-coding regions is involved in the susceptibility to severe phenotypes of male infertility

Detalhes bibliográficos
Autor(a) principal: IVIRMA Group
Data de Publicação: 2022
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
Texto Completo: http://hdl.handle.net/10362/144375
Resumo: © 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.
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network_name_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository_id_str https://opendoar.ac.uk/repository/7160
spelling Common genetic variation in KATNAL1 non-coding regions is involved in the susceptibility to severe phenotypes of male infertilityAnimalsAzoospermia/geneticsHumansInfertility, Male/geneticsKatanin/geneticsMaleNucleotidesOligospermia/geneticsPhenotypePolymorphism, Single NucleotideProtein Isoforms/geneticsSemenSpermatogenesis/genetics© 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.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.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centre for Toxicogenomics and Human Health (ToxOmics)RUNIVIRMA Group2022-09-28T22:50:43Z2022-102022-10-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article12application/pdfhttp://hdl.handle.net/10362/144375eng2047-2919PURE: 46785851https://doi.org/10.1111/andr.13221info:eu-repo/semantics/openAccessreponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiainstacron:RCAAP2024-05-22T18:05:44Zoai:run.unl.pt:10362/144375Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireinfo@rcaap.ptopendoar:https://opendoar.ac.uk/repository/71602025-05-28T17:36:11.977089Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologiafalse
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
IVIRMA Group
Animals
Azoospermia/genetics
Humans
Infertility, Male/genetics
Katanin/genetics
Male
Nucleotides
Oligospermia/genetics
Phenotype
Polymorphism, Single Nucleotide
Protein Isoforms/genetics
Semen
Spermatogenesis/genetics
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 IVIRMA Group
author_facet IVIRMA Group
author_role author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Centre for Toxicogenomics and Human Health (ToxOmics)
RUN
dc.contributor.author.fl_str_mv IVIRMA Group
dc.subject.por.fl_str_mv Animals
Azoospermia/genetics
Humans
Infertility, Male/genetics
Katanin/genetics
Male
Nucleotides
Oligospermia/genetics
Phenotype
Polymorphism, Single Nucleotide
Protein Isoforms/genetics
Semen
Spermatogenesis/genetics
topic Animals
Azoospermia/genetics
Humans
Infertility, Male/genetics
Katanin/genetics
Male
Nucleotides
Oligospermia/genetics
Phenotype
Polymorphism, Single Nucleotide
Protein Isoforms/genetics
Semen
Spermatogenesis/genetics
description © 2022 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.
publishDate 2022
dc.date.none.fl_str_mv 2022-09-28T22:50:43Z
2022-10
2022-10-01T00:00:00Z
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/10362/144375
url http://hdl.handle.net/10362/144375
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2047-2919
PURE: 46785851
https://doi.org/10.1111/andr.13221
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 12
application/pdf
dc.source.none.fl_str_mv reponame:Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
instname:FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron:RCAAP
instname_str FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
instacron_str RCAAP
institution RCAAP
reponame_str Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
collection Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
repository.name.fl_str_mv Repositórios Científicos de Acesso Aberto de Portugal (RCAAP) - FCCN, serviços digitais da FCT – Fundação para a Ciência e a Tecnologia
repository.mail.fl_str_mv info@rcaap.pt
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