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| Home > Articles > Published articles > Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility |
| Home > Articles > Published articles > Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility |
(Instituto de Investigación Sanitaria de Granada) (Institute of Reproductive Genetics. University of Münster) (Center for Predictive and Preventive Genetics. Institute for Cell and Molecular Biology. University of Porto) (Instituto de Investigación Sanitaria de Granada) (Instituto de Investigación Sanitaria La Fe (València)) (Instituto de Investigación Sanitaria La Fe (València)) (Department of Obstetrics and Gynecology. Faculty of Medicine. University of Lisbon) (CEIFER Biobanco - GAMETIA) (UGC de Obstetricia y Ginecología. Complejo Hospitalario de Jaén) (Instituto de Investigación Sanitaria de Granada) (Universidad de Granada. Departamento de Genética) (Universidad de Granada. Departamento de Genética) (Instituto de Investigación Sanitaria La Fe) (Centro Hospitalar Universitário de Lisboa Norte) (Centro Hospitalar Universitário de Lisboa Norte) (Institut d'Investigació Biomèdica Sant Pau) (Instituto de Parasitología y Biomedicina "López-Neyra") (Serviço de Genética. Departamento de Patologia. Faculdade de Medicina. Universidade do Porto) (Serviço de Genética. Departamento de Patologia. Faculdade de Medicina. Universidade do Porto) (Institut d'Investigació Biomèdica Sant Pau) (Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP)) (ToxOmics - Centro de Toxicogenómica e Saúde Humana. Nova Medical School) (Institut d'Investigació Biomèdica de Bellvitge) (University Hospital Münster. Department of Clinical and Surgical Andrology. Centre of Reproductive Medicine and Andrology) (Universidad de Granada. Departamento de Bioquímica y Biología Molecular) (Instituto de Investigación Sanitaria de Granada)| Date: | 2022 |
| Abstract: | 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. |
| Grants: | European Commission B-CTS-584-UGR20 European Commission FPU20/02926 Ministerio de Ciencia e Innovación SAF2016-78722-R Ministerio de Ciencia e Innovación PID2020-120157RB-I00 Agencia Estatal de Investigación RYC-2014-16458 Agencia Estatal de Investigación BES-2017-081222 Instituto de Salud Carlos III DTS18/00101 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017/SGR-191 Agència de Gestió d'Ajuts Universitaris i de Recerca CES09/020 |
| Note: | Altres ajuts: Andalusian Plan for Research and Innovation (PAIDI 2020) (ref. PY20_00212); R+D+i Projects of the FEDER Operational Programme 2020; Portuguese Foundation for Science and Technology (FCT) (projects PEstC/SAU/LA0003/2013, POCI-01-0145-FEDER-007274); Portuguese Government (FCT projects IF/01262/2014, UID/BIM/00009/2013, UIDB/UIDP/00009/2020); Portuguese State Budget of the Ministry for Science, Technology and High Education (SFRH/BPD/120777/2016); SNS-Departament de Salut, Generalitat de Catalunya; German Research Foundation Clinical Research Unit 'Male Germ Cells' (DFG CRU326). |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Subject: | Alleles ; Genome-Wide Association Study ; Humans ; Infertility, Male ; Intracellular Signaling Peptides and Proteins ; Male ; Protein Serine-Threonine Kinases ; Sertoli Cells ; Spermatogenesis |
| Published in: | Communications Biology, Vol. 5 Núm. 1 (december 2022) , p. 1220, ISSN 2399-3642 |
