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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\u2013testis 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\u20132.93), ORaddrs2233678 = 1.62 (1.11\u20132.36), ORaddrs62105751 = 1.43 (1.06\u20131.93)). 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.<\/jats:p>","DOI":"10.3390\/jpm12060932","type":"journal-article","created":{"date-parts":[[2022,6,4]],"date-time":"2022-06-04T09:42:32Z","timestamp":1654335752000},"page":"932","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Common Variation in the PIN1 Locus Increases the Genetic Risk to Suffer from Sertoli Cell-Only Syndrome"],"prefix":"10.3390","volume":"12","author":[{"given":"Miriam","family":"Cerv\u00e1n-Mart\u00edn","sequence":"first","affiliation":[{"name":"Departamento de Gen\u00e9tica e Instituto de Biotecnolog\u00eda, Centro de Investigaci\u00f3n Biom\u00e9dica, Universidad de Granada, Armilla, 18100 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, 18012 Granada, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5471-5824","authenticated-orcid":false,"given":"Lara","family":"Bossini-Castillo","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Instituto de Biotecnolog\u00eda, Centro de Investigaci\u00f3n Biom\u00e9dica, Universidad de Granada, Armilla, 18100 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, 18012 Granada, Spain"}]},{"given":"Andrea","family":"Guzm\u00e1n-Jimenez","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Instituto de Biotecnolog\u00eda, Centro de Investigaci\u00f3n Biom\u00e9dica, Universidad de Granada, Armilla, 18100 Granada, Spain"}]},{"given":"Roc\u00edo","family":"Rivera-Egea","sequence":"additional","affiliation":[{"name":"Andrology Laboratory and Sperm Bank, IVIRMA Valencia, 46015 Valencia, Spain"},{"name":"IVI Foundation, Health Research Institute La Fe, 46026 Valencia, Spain"}]},{"given":"Nicol\u00e1s","family":"Garrido","sequence":"additional","affiliation":[{"name":"IVI Foundation, Health Research Institute La Fe, 46026 Valencia, Spain"},{"name":"Servicio de Urolog\u00eda, Hospital Universitari i Politecnic La Fe e Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5005-3325","authenticated-orcid":false,"given":"Saturnino","family":"Luj\u00e1n","sequence":"additional","affiliation":[{"name":"Servicio de Urolog\u00eda, Hospital Universitari i Politecnic La Fe e Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6365-1087","authenticated-orcid":false,"given":"Gema","family":"Romeu","sequence":"additional","affiliation":[{"name":"Servicio de Urolog\u00eda, Hospital Universitari i Politecnic La Fe e Instituto de Investigaci\u00f3n Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain"}]},{"given":"Samuel","family":"Santos-Ribeiro","sequence":"additional","affiliation":[{"name":"IVI-RMA Lisbon, 1800-282 Lisbon, Portugal"},{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, University of Lisbon, 1649-028 Lisbon, Portugal"}]},{"name":"IVIRMA Group","sequence":"additional","affiliation":[]},{"name":"Lisbon Clinical Group","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2185-565X","authenticated-orcid":false,"given":"Jos\u00e9 A.","family":"Castilla","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, 18012 Granada, Spain"},{"name":"Unidad de Reproducci\u00f3n, UGC Obstetricia y Ginecolog\u00eda, HU Virgen de las Nieves, 18014 Granada, Spain"},{"name":"CEIFER-GAMETIA Biobank, 18004 Granada, Spain"}]},{"given":"M. Carmen","family":"Gonzalvo","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, 18012 Granada, Spain"},{"name":"Unidad de Reproducci\u00f3n, UGC Obstetricia y Ginecolog\u00eda, HU Virgen de las Nieves, 18014 Granada, Spain"}]},{"given":"Ana","family":"Clavero","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, 18012 Granada, Spain"},{"name":"Unidad de Reproducci\u00f3n, UGC Obstetricia y Ginecolog\u00eda, HU Virgen de las Nieves, 18014 Granada, Spain"}]},{"given":"F. Javier","family":"Vicente","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, 18012 Granada, Spain"},{"name":"UGC de Urolog\u00eda, HU Virgen de las Nieves, 18014 Granada, Spain"}]},{"given":"Vicente","family":"Maldonado","sequence":"additional","affiliation":[{"name":"UGC de Obstetricia y Ginecolog\u00eda, Complejo Hospitalario de Ja\u00e9n, 23007 Ja\u00e9n, Spain"}]},{"given":"Sara","family":"Gonz\u00e1lez-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Instituto de Biotecnolog\u00eda, Centro de Investigaci\u00f3n Biom\u00e9dica, Universidad de Granada, Armilla, 18100 Granada, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5413-1581","authenticated-orcid":false,"given":"Inmaculada","family":"Rodr\u00edguez-Mart\u00edn","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Instituto de Biotecnolog\u00eda, Centro de Investigaci\u00f3n Biom\u00e9dica, 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David","family":"Carmona","sequence":"additional","affiliation":[{"name":"Departamento de Gen\u00e9tica e Instituto de Biotecnolog\u00eda, Centro de Investigaci\u00f3n Biom\u00e9dica, Universidad de Granada, Armilla, 18100 Granada, Spain"},{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, 18012 Granada, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3507-343X","authenticated-orcid":false,"given":"Rogelio J.","family":"Palomino-Morales","sequence":"additional","affiliation":[{"name":"Instituto de Investigaci\u00f3n Biosanitaria ibs.GRANADA, 18012 Granada, Spain"},{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular I, Universidad de Granada, 18071 Granada, Spain"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"aac4354","DOI":"10.1126\/science.aac4354","article-title":"In vivo aspects of protein folding and quality control","volume":"353","author":"Balchin","year":"2016","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1042\/EBC20190042","article-title":"Uncovering protein structure","volume":"64","author":"Stollar","year":"2020","journal-title":"Essays Biochem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41580-020-0250-z","article-title":"Mechanisms, regulation and functions of the unfolded protein response","volume":"21","author":"Hetz","year":"2020","journal-title":"Nat. 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