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Effect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohort

2021-07Journal article Restricted access
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dc.contributor.authorCerván‐Martín, Miriam
dc.contributor.authorBossini‐Castillo, Lara
dc.contributor.authorRivera‐Egea, Rocío
dc.contributor.authorGarrido, Nicolás
dc.contributor.authorLuján, Saturnino
dc.contributor.authorRomeu, Gema
dc.contributor.authorSantos‐Ribeiro, Samuel
dc.contributor.authorIVIRMA Group, Lisbon Clinical Group
dc.contributor.authorCastilla, José A.
dc.contributor.authorGonzalvo, María del Carmen
dc.contributor.authorClavero, Ana
dc.contributor.authorVicente, Francisco Javier
dc.contributor.authorGuzmán‐Jiménez, Andrea
dc.contributor.authorBurgos, Miguel
dc.contributor.authorBarrionuevo, Francisco Javier
dc.contributor.authorJiménez, Rafael
dc.contributor.authorSánchez‐Curbelo, Josvany
dc.contributor.authorLópez‐Rodrigo, Olga
dc.contributor.authorPeraza, María Fernanda
dc.contributor.authorPereira‐Caetano, Iris
dc.contributor.authorMarques, Patrícia Isabel
dc.contributor.authorCarvalho, Filipa
dc.contributor.authorBarros, Alberto
dc.contributor.authorBassas, Luís
dc.contributor.authorSeixas, Susana
dc.contributor.authorGonçalves, João
dc.contributor.authorLarriba, Sara
dc.contributor.authorLopes, Alexandra Manuel
dc.contributor.authorCarmona, Francisco David
dc.contributor.authorPalomino‐Morales, Rogelio Jesús
dc.date.accessioned2022-02-03T16:43:45Z
dc.date.available2022-02-03T16:43:45Z
dc.date.issued2021-07
dc.descriptionIVIRMA 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 Correiapt_PT
dc.description.abstractBackground: 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.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationAndrology. 2021 Jul;9(4):1151-1165. doi: 10.1111/andr.13009. Epub 2021 Apr 20.pt_PT
dc.identifier.doi10.1111/andr.13009pt_PT
dc.identifier.issn2047-2919
dc.identifier.urihttp://hdl.handle.net/10400.18/7922
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWiley/ American Society of Andrology and European Academy of Andrologypt_PT
dc.relationCentre for Toxicogenomics and Human Health
dc.relationUnderstanding the basis of semen hyperviscosity and asthenozoospermia phenotypes - a systems biology approach
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/doi/10.1111/andr.13009pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectSpermatogenesispt_PT
dc.subjectMale Infertilitypt_PT
dc.subjectAzoospermiapt_PT
dc.subjectSevere Oligozoospermiapt_PT
dc.subjectNon-obstructive Azoospermiapt_PT
dc.subjectDoenças Genéticaspt_PT
dc.titleEffect and in silico characterization of genetic variants associated with severe spermatogenic disorders in a large Iberian cohortpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleCentre for Toxicogenomics and Human Health
oaire.awardTitleUnderstanding the basis of semen hyperviscosity and asthenozoospermia phenotypes - a systems biology approach
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UIDB%2F00009%2F2020/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F120777%2F2016/PT
oaire.citation.endPage1165pt_PT
oaire.citation.issue4pt_PT
oaire.citation.startPage1151pt_PT
oaire.citation.titleAndrologypt_PT
oaire.citation.volume9pt_PT
oaire.fundingStream6817 - DCRRNI ID
person.familyNameGonçalves
person.givenNameJoão
person.identifier.ciencia-id5710-1FAE-5FAB
person.identifier.orcid0000-0001-9359-8774
person.identifier.ridL-2265-2014
person.identifier.scopus-author-id55934387500
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.embargofctAcesso de acordo com política editorial da revista.pt_PT
rcaap.rightsembargoedAccesspt_PT
rcaap.typearticlept_PT
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