Journal of Personalized Medicine (Jun 2022)
Common Variation in the PIN1 Locus Increases the Genetic Risk to Suffer from Sertoli Cell-Only Syndrome
- Miriam Cerván-Martín,
- Lara Bossini-Castillo,
- Andrea Guzmán-Jimenez,
- Rocío Rivera-Egea,
- Nicolás Garrido,
- Saturnino Luján,
- Gema Romeu,
- Samuel Santos-Ribeiro,
- IVIRMA Group,
- Lisbon Clinical Group,
- José A. Castilla,
- M. Carmen Gonzalvo,
- Ana Clavero,
- F. Javier Vicente,
- Vicente Maldonado,
- Sara González-Muñoz,
- Inmaculada Rodríguez-Martín,
- Miguel Burgos,
- Rafael Jiménez,
- Maria Graça Pinto,
- Isabel Pereira,
- Joaquim Nunes,
- Josvany Sánchez-Curbelo,
- Olga López-Rodrigo,
- Iris Pereira-Caetano,
- Patricia Isabel Marques,
- Filipa Carvalho,
- Alberto Barros,
- Lluís Bassas,
- Susana Seixas,
- João Gonçalves,
- Sara Larriba,
- Alexandra M. Lopes,
- F. David Carmona,
- Rogelio J. Palomino-Morales
Affiliations
- Miriam Cerván-Martín
- Departamento de Genética e Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Armilla, 18100 Granada, Spain
- Lara Bossini-Castillo
- Departamento de Genética e Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Armilla, 18100 Granada, Spain
- Andrea Guzmán-Jimenez
- Departamento de Genética e Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Armilla, 18100 Granada, Spain
- Rocío Rivera-Egea
- Andrology Laboratory and Sperm Bank, IVIRMA Valencia, 46015 Valencia, Spain
- Nicolás Garrido
- IVI Foundation, Health Research Institute La Fe, 46026 Valencia, Spain
- Saturnino Luján
- Servicio de Urología, Hospital Universitari i Politecnic La Fe e Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain
- Gema Romeu
- Servicio de Urología, Hospital Universitari i Politecnic La Fe e Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain
- Samuel Santos-Ribeiro
- IVI-RMA Lisbon, 1800-282 Lisbon, Portugal
- IVIRMA Group
- Lisbon Clinical Group
- José A. Castilla
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
- M. Carmen Gonzalvo
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
- Ana Clavero
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
- F. Javier Vicente
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
- Vicente Maldonado
- UGC de Obstetricia y Ginecología, Complejo Hospitalario de Jaén, 23007 Jaén, Spain
- Sara González-Muñoz
- Departamento de Genética e Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Armilla, 18100 Granada, Spain
- Inmaculada Rodríguez-Martín
- Departamento de Genética e Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Armilla, 18100 Granada, Spain
- Miguel Burgos
- Departamento de Genética e Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Armilla, 18100 Granada, Spain
- Rafael Jiménez
- Departamento de Genética e Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Armilla, 18100 Granada, Spain
- Maria Graça Pinto
- Centro de Medicina Reprodutiva, Maternidade Alfredo da Costa, Centro Hospitalar Universitário de Lisboa Central, 2890-045 Lisbon, Portugal
- Isabel Pereira
- Departamento de Obstetrícia, Ginecologia e Medicina da Reprodução, Hospital de Santa Maria, Centro Hospitalar Universitário de Lisboa Norte, 1649-028 Lisbon, Portugal
- Joaquim Nunes
- Departamento de Obstetrícia, Ginecologia e Medicina da Reprodução, Hospital de Santa Maria, Centro Hospitalar Universitário de Lisboa Norte, 1649-028 Lisbon, Portugal
- Josvany Sánchez-Curbelo
- Laboratory of Seminology and Embryology, Andrology Service-Fundació Puigvert, 08025 Barcelona, Spain
- Olga López-Rodrigo
- Laboratory of Seminology and Embryology, Andrology Service-Fundació Puigvert, 08025 Barcelona, Spain
- Iris Pereira-Caetano
- Departamento de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge, 1600-609 Lisbon, Portugal
- Patricia Isabel Marques
- i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
- Filipa Carvalho
- i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
- Alberto Barros
- i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
- Lluís Bassas
- Laboratory of Seminology and Embryology, Andrology Service-Fundació Puigvert, 08025 Barcelona, Spain
- Susana Seixas
- i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
- João Gonçalves
- Departamento de Genética Humana, Instituto Nacional de Saúde Dr. Ricardo Jorge, 1600-609 Lisbon, Portugal
- Sara Larriba
- Human Molecular Genetics Group, Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, 08908 Barcelona, Spain
- Alexandra M. Lopes
- i3S—Instituto de Investigação e Inovação em Saúde, Universidade do Porto, 4200-135 Porto, Portugal
- F. David Carmona
- Departamento de Genética e Instituto de Biotecnología, Centro de Investigación Biomédica, Universidad de Granada, Armilla, 18100 Granada, Spain
- Rogelio J. Palomino-Morales
- Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain
- DOI
- https://doi.org/10.3390/jpm12060932
- Journal volume & issue
-
Vol. 12,
no. 6
p. 932
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 (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.
Keywords
- severe spermatogenic failure
- male infertility
- PIN1
- single-nucleotide polymorphism
- Sertoli cell-only syndrome