Cervan-Martin, MiriamBossini-Castillo, LaraGuzman-Jimenez, AndreaRivera-Egea, RocioGarrido, NicolasLujan, SaturninoRomeu, GemaSantos-Ribeiro, SamuelLisbon Clinical Group,Castilla, Jose AGonzalvo, M CarmenClavero, AnaVicente, F JavierMaldonado, VicenteGonzalez-Muñoz, SaraRodriguez-Martin, InmaculadaBurgos, MiguelJimenez, RafaelPinto, Maria GraçaPereira, IsabelNunes, JoaquimSanchez-Curbelo, JosvanyLopez-Rodrigo, OlgaPereira-Caetano, IrisMarques, Patricia IsabelCarvalho, FilipaBarros, AlbertoBassas, LluisSeixas, SusanaGonçalves, JoãoLarriba, SaraLopes, Alexandra MCarmona, F DavidPalomino-Morales, Rogelio J2023-05-032023-05-032022-05-30Cerván-Martín M, Bossini-Castillo L, Guzmán-Jimenez A, Rivera-Egea R, Garrido N, Luján S, et al. Common Variation in the PIN1 Locus Increases the Genetic Risk to Suffer from Sertoli Cell-Only Syndrome. J Pers Med. 2022 Jun 4;12(6):932.2075-4426http://hdl.handle.net/10668/21383We 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.enAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/PIN1Sertoli cell-only syndromemale infertilitysevere spermatogenic failuresingle-nucleotide polymorphismCell ProliferationStem CellsProtein IsoformsGene ExpressionSertoli Cell-Only SyndromeInfertility, MaleGenotypePolymorphism, Single NucleotideBlood-Testis BarrierLogistic ModelsSertoli CellsOligospermiaAllelesPeptidylprolyl IsomeraseTranscription FactorsAzoospermiaresearch article35743717open accessAlelosAzoospermiaOligospermiaBarrera hematotesticularCélulas madreCélulas de sertoliExpresión génicaFactores de transcripciónInfertilidad masculinaIsoformas de proteínasGenotipo10.3390/jpm12060932PMC9225465https://www.mdpi.com/2075-4426/12/6/932/pdf?version=1655111578https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9225465/pdf