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

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 wer...

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Detalles Bibliográficos
Autores: Cervan-Martin, M, Tuttelmann, F, Lopes, AM, Bossini-Castillo, L, Rivera-Egea, R, Garrido, N, Lujan, S, Romeu, G, Santos-Ribeiro, S, Castilla, JA, Gonzalvo, MC, Clavero, A, Maldonado, V, Vicente, FJ, Gonzalez-Munoz, S, Guzman-Jimenez, A, Burgos, M, Jimenez, R, Pacheco, A, Gonzalez, C, Gomez, S, Amoros, D, Aguilar, J, Quintana, F, Calhaz-Jorge, C, Aguiar, A, Nunes, J, Sousa, S, Pereira, I, Pinto, MG, Correia, S, Sanchez-Curbelo, J, Lopez-Rodrigo, O, Martin, J, Pereira-Caetano, I, Marques, PI, Carvalho, F, Barros, A, Gromoll, J, Bassas, L, Seixas, S, Goncalves, J, Larriba, S, Kliesch, S, Palomino-Morales, RJ, Carmona, FD
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau)
Repositorio:r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau
OAI Identifier:oai:iibsantpau.fundanetsuite.com:p14878
Acceso en línea:https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=14878
https://ddd.uab.cat/record/277665
Access Level:acceso abierto
Palabra clave:signal peptide
VRK1 protein, human
allele
genetics
genome-wide association study
human
male
male infertility
metabolism
Sertoli cell
spermatogenesis
Alleles
Genome-Wide Association Study
Humans
Infertility, Male
Intracellular Signaling Peptides and Proteins
Male
Protein Serine-Threonine Kinases
Sertoli Cells
Spermatogenesis
Descripción
Sumario: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-DR beta 1 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. A GWAS in a large case-control cohort of European ancestry identifies two genomic regions, the MHC class II gene HLA-DRB1 and an upstream locus of VRK1, that are associated with the most severe phenotype of spermatogenic failure.

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