guest ::
| Home > Articles > Published articles > Common Variation in the PIN1 Locus Increases the Genetic Risk to Suffer from Sertoli Cell-Only Syndrome |
| Home > Articles > Published articles > Common Variation in the PIN1 Locus Increases the Genetic Risk to Suffer from Sertoli Cell-Only Syndrome |
(Instituto de Investigación Sanitaria de Granada) (Instituto de Investigación Sanitaria de Granada) (Instituto de Investigación Sanitaria La Fe) (Instituto de Investigación Sanitaria La Fe) (Instituto de Investigación Sanitaria La Fe) (Department of Obstetrics and Gynecology. Faculty of Medicine. University of Lisbon) (CEIFER-GAMETIA Biobank) (UGC de Obstetricia y Ginecología. Complejo Hospitalario de Jaén) (Universidad de Granada. Departamento de Genética) (Universidad de Granada. Departamento de Genética) (Centro Hospitalar Universitário de Lisboa Norte) (Institut d'Investigació Biomèdica Sant Pau) (Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP)) (Serviço de Genética. Departamento de Patologia. Faculdade de Medicina da Universidade do Porto) (Serviço de Genética. Departamento de Patologia. Faculdade de Medicina da 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) (Instituto de Investigación Sanitaria de Granada) (Universidad de Granada. Departamento de Bioquímica y Biología Molecular)
| Date: | 2022 |
| Abstract: | We aimed to analyze the role of the common genetic variants located in the PIN1 locus, a relevant prolyl isomerase required to control the proliferation of spermatogonial stem cells and the integrity of the blood-testis barrier, in the genetic risk of developing male infertility due to a severe spermatogenic failure (SPGF). Genotyping was performed using TaqMan genotyping assays for three PIN1 taggers (rs2287839, rs2233678 and rs62105751). The study cohort included 715 males diagnosed with SPGF and classified as suffering from non-obstructive azoospermia (NOA, n = 505) or severe oligospermia (SO, n = 210), and 1058 controls from the Iberian Peninsula. The allelic frequency differences between cases and controls were analyzed by the means of logistic regression models. A subtype specific genetic association with the subset of NOA patients classified as suffering from the Sertoli cell-only (SCO) syndrome was observed with the minor alleles showing strong risk effects for this subset (ORrs2287839 = 1. 85 (1. 17-2. 93), ORrs2233678 = 1. 62 (1. 11-2. 36), ORrs62105751 = 1. 43 (1. 06-1. 93)). The causal variants were predicted to affect the binding of key transcription factors and to produce an altered PIN1 gene expression and isoform balance. In conclusion, common non-coding single-nucleotide polymorphisms located in PIN1 increase the genetic risk to develop SCO. |
| Grants: | Ministerio de Economía y Competitividad SAF2016-78722-R Ministerio de Economía y Competitividad PID2020-120157RB-I00 Ministerio de Economía y Competitividad IJC2018-038026-I Ministerio de Economía y Competitividad MCIN/AEI/10.13039/501100011033 Ministerio de Educación, Cultura y Deporte FPU20/02926 European Commission B-CTS-584-UGR20 European Commission B-CTS-260-UGR20 Instituto de Salud Carlos III RYC-2014-16458 Instituto de Salud Carlos III DTS18/00101 Agència de Gestió d'Ajuts Universitaris i de Recerca 2017SGR191 Agència de Gestió d'Ajuts Universitaris i de Recerca CES09/020 Agencia Estatal de Investigación BES-2017-081222 |
| Note: | Altres ajuts: Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020) (ref. PY20_00212, P20_00583); the Portuguese Foundation for Science and Technology (FCT); European Social Funds (COMPETE-FEDER); National Funds (PEstC/SAU/LA0003/2013, POCI-01-0145-FEDER-007274); Portuguese Government FCT (IF/01262/2014); FCT post-doctoral fellowship (SFRH/BPD/120777/2016); the Portuguese State Budget of the Ministry for Science, Technology and High Education; FCT (UID/BIM/00009/2013, UIDB/UIDP/00009/2020); European Regional Development Fund (ERDF)"a way to build Europe"; Generalitat de Catalunya; FSE "El FSE invierte en tu futuro"). |
| 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: | Severe spermatogenic failure ; Male infertility ; PIN1 ; Single-nucleotide polymorphism ; Sertoli cell-only syndrome |
| Published in: | Journal of personalized medicine, Vol. 12 Núm. 6 (june 2022) , p. 932, ISSN 2075-4426 |
