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. 2022 Jun 4;12(6):932.
doi: 10.3390/jpm12060932.

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

Miriam Cerván-Martín  1   2 , Lara Bossini-Castillo  1   2 , Andrea Guzmán-Jimenez  1 , Rocío Rivera-Egea  3   4 , Nicolás Garrido  4   5 , Saturnino Luján  5 , Gema Romeu  5 , Samuel Santos-Ribeiro  6   7 , Ivirma Group, Lisbon Clinical Group, José A Castilla  2   8   9 , M Carmen Gonzalvo  2   8 , Ana Clavero  2   8 , F Javier Vicente  2   10 , Vicente Maldonado  11 , Sara González-Muñoz  1 , Inmaculada Rodríguez-Martín  1   12 , Miguel Burgos  1 , Rafael Jiménez  1 , Maria Graça Pinto  13 , Isabel Pereira  14 , Joaquim Nunes  14 , Josvany Sánchez-Curbelo  15 , Olga López-Rodrigo  15 , Iris Pereira-Caetano  16 , Patricia Isabel Marques  17   18 , Filipa Carvalho  17   19 , Alberto Barros  17   19 , Lluís Bassas  15 , Susana Seixas  17   18 , João Gonçalves  16   20 , Sara Larriba  21 , Alexandra M Lopes  17   18 , F David Carmona  1   2 , Rogelio J Palomino-Morales  2   22
Affiliations

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

Miriam Cerván-Martín et al. J Pers Med. .

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: PIN1; Sertoli cell-only syndrome; male infertility; severe spermatogenic failure; single-nucleotide polymorphism.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Genetic and functional structure of the PIN1 region. Linkage disequilibrium patterns in the European population included in the 1000 Genome Project were retrieved from the LDlink repository to design a tag-SNP study for the PIN1 locus. The selected tag-SNPs are highlighted in red. All SNP positions are reported in GRCh38. PIN1-DT: PIN1 divergent transcript.
Figure 2
Figure 2
Analysis of data from the GTEx repository to detect QTL effects and isoform expression patterns in the PIN1 locus. (A) Expression-QTL (eQTL) and (B) splicing-QTL (sQTL) allele effects on PIN1 of the rs3810166 variant. (C) PIN1 transcript expression in human testis and brain tissues. The sQTL-affected intron is highlighted in red. The transcript ENST00000591777.1 is marked with a red arrow. NES: normalized effect size.
See this image and copyright information in PMC

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