Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility

• Autor(a) principal: Cerván-Martín, Miriam
• Data de Publicação: 2022
• Outros Autores: Tüttelmann, Frank, Lopes, Alexandra M., Bossini-Castillo, Lara, Rivera-Egea, Rocío, Garrido, Nicolás, Lujan, Saturnino, Romeu, Gema, Santos-Ribeiro, Samuel, Castilla, José A., Carmen Gonzalvo, M., Clavero, Ana, Maldonado, Vicente, Vicente, F. Javier, González-Muñoz, Sara, Guzmán-Jiménez, Andrea, Burgos, Miguel, Jiménez, Rafael, Pacheco, Alberto, González, Cristina, Gómez, Susana, Amorós, David, Aguilar, Jesus, Quintana, Fernando, Calhaz-Jorge, Carlos, Aguiar, Ana, Nunes, Joaquim, Sousa, Sandra, Pereira, Isabel, Pinto, Maria Graça, Correia, Sónia, Sánchez-Curbelo, Josvany, López-Rodrigo, Olga, Martín, Javier, Pereira-Caetano, Iris, Marques, Patricia I., Carvalho, Filipa, Barros, Alberto, Gromoll, Jörg, Bassas, Lluís, Seixas, Susana, Gonçalves, João, Larriba, Sara, Kliesch, Sabine, Palomino-Morales, Rogelio J., Carmona, F. David
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10400.18/8572
• topic: Alleles; Genome-Wide Association Study; Spermatogenesis; Infertility, Male; Genetics; Metabolism Male; Intracellular Signaling Peptides and Proteins; Protein Serine-Threonine Kinases; Sertoli Cells; Doenças Genéticas

We conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pattern of SPGF, defined by Sertoli cell-only (SCO) phenotype, namely the MHC class II gene HLA-DRB1 (rs1136759, P = 1.32E-08, OR = 1.80) and an upstream locus of VRK1 (rs115054029, P = 4.24E-08, OR = 3.14), which encodes a protein kinase involved in the regulation of spermatogenesis. The SCO-associated rs1136759 allele (G) determines a serine in the position 13 of the HLA-DRβ1 molecule located in the antigen-binding pocket. Overall, our data support the notion of unexplained SPGF as a complex trait influenced by common variation in the genome, with the SCO phenotype likely representing an immune-mediated condition.