Common Variation in the PIN1 Locus Increases the Genetic Risk to Suffer from Sertoli Cell-Only Syndrome

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 sper...

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Detalles Bibliográficos
Autores: Cerván Martín, Miriam, Bossini Castillo, Lara, Guzmán Jimenez, Andrea, Rivera Egea, Rocío, Garrido, Nicolás, Luján, Saturnino, Romeu, Gema, Santos Ribeiro, Samuel, Castilla, José A., Gonzalvo, M. Carmen, Clavero, Ana, Vicente, F. Javier, Maldonado, Vicente, González Muñoz, Sara, Rodríguez Martín, Inmaculada, Burgos, Miguel, Jiménez, Rafael, Pinto, Maria Graça, Pereira, Isabel, Nunes, Joaquim, Sánchez Curbelo, Josvany, López Rodrigo, Olga, Pereira Caetano, Iris, Marques, Patricia Isabel, Carvalho, Filipa, Barros, Alberto, Bassas, Lluís, Seixas, Susana, Gonçalves, João, Larriba, Sara, Lopes, Alexandra M., Carmona, F. David, Palomino Morales, Rogelio J.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/187824
Acceso en línea:https://hdl.handle.net/2445/187824
Access Level:acceso abierto
Palabra clave:Esterilitat masculina
Polimorfisme genètic
Male sterility
Genetic polymorphisms
Descripción
Sumario: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 (OR(add)rs2287839 = 1.85 (1.17-2.93), OR(add)rs2233678 = 1.62 (1.11-2.36), OR(add)rs62105751 = 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.

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