Common Variation in the PIN1 Locus Increases the Genetic Risk to Suffer from Sertoli Cell-Only Syndrome
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AuthorCerván Martín, Miriam; Bossini Castillo, Lara María; Guzmán Jiménez, Andrea; Castilla Alcalá, José Antonio; Gonzalvo, M. Carmen; Clavero, Ana; Vicente Prados, Francisco Javier; González Muñoz, Sara; Rodríguez Martín, Inmaculada; Burgos Poyatos, Miguel; Jiménez Medina, Rafael; Carmona López, Francisco David; Palomino Morales, Rogelio Jesús; IVIRMA Group; Lisbon Clinical Group
Severe spermatogenic failureMale infertilityPIN1Single nucleotide polymorphismSertoli cell-only syndrome
Cerván-Martín, M... [et al.]. Common Variation in the PIN1 Locus Increases the Genetic Risk to Suffer from Sertoli Cell-Only Syndrome. J. Pers. Med. 2022, 12, 932. [https://doi.org/10.3390/jpm12060932]
SponsorshipPlan Andaluz de Investigacion, Desarrollo e Innovacion (PAIDI 2020) PY20_00212 P20_00583; Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation SAF2016-78722-R PID2020-120157RB-I00; Proyectos I + D + i del Programa Operativo FEDER 2020 B-CTS-584-UGR20 B-CTS-260-UGR20; Spanish Government RYC-2014-16458; Spanish Ministry of Economy and Competitiveness through the "Juan de la Cierva Incorporacion" program (MCIN/AEI) IJC2018038026-I; European Commission; MCIN/AEI; FSE "El FSE invierte en tu futuro" FPU20/02926 BES-2017-081222; Portuguese Foundation for Science and Technology (FCT) - European Social Funds (COMPETE-FEDER) Portuguese Foundation for Science and Technology IF/01262/2014; FCT from the Portuguese State Budget of the Ministry for Science, Technology and High Education SFRH/BPD/120777/2016; European Social Fund through the Programa Operacional do Capital Humano; Portuguese Foundation for Science and Technology European Commission UID/BIM/00009/2013 UIDB/UIDP/00009/2020; Instituto de Salud Carlos III (FEDER funds/European Regional Development Fund (ERDF)-a way to build Europe) DTS18/00101; Generalitat de Catalunya 2017SGR191; SNS-Dpt. Salut Generalitat de Catalunya CES09/020 MCIN/AEI BES-2017-081222 PEstC/SAU/LA0003/2013 POCI-01-0145-FEDER-007274
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 (ORaddrs2287839 = 1.85 (1.17–2.93), ORaddrs2233678 = 1.62 (1.11–2.36), ORaddrs62105751 = 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.