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

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

Fecha de publicación: Fecha Ahead of Print:

Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Cerván-Martín, M
  • Tüttelmann, F
  • Lopes, AM
  • Bossini-Castillo, L
  • Rivera-Egea, R
  • Romeu, G
  • Santos-Ribeiro, S
  • Castilla, JA
  • Carmen Gonzalvo, M.
  • Clavero, A
  • Maldonado, V
  • Vicente, FJ
  • González-Muñoz, S
  • Guzmán-Jiménez, A
  • Burgos, M
  • Jiménez, R
  • Pacheco, A
  • González, C
  • Gómez, S
  • Amorós, D
  • Aguilar, J
  • Quintana, F
  • Calhaz-Jorge, C
  • Aguiar, A
  • Nunes, J
  • Sousa, S
  • Pereira, I
  • Pinto, MG
  • Correia, S
  • Sánchez-Curbelo, J
  • López-Rodrigo, O
  • Martín, J
  • Pereira-Caetano, I
  • Marques, PI
  • Carvalho, F
  • Barros, A
  • Gromoll, J
  • Bassas, L
  • Seixas, S
  • Goncalves, Joao
  • Larriba, S
  • Kliesch, S
  • Palomino-Morales, RJ
  • Carmona, FD

Grupos

Abstract

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.

© 2022. The Author(s).

Datos de la publicación

ISSN/ISSNe:
2399-3642, 2399-3642

Communications Biology  NATURE PORTFOLIO

Tipo:
Article
Páginas:
1220-1220
PubMed:
36357561
Factor de Impacto:
2,256 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 13

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Keywords

  • FOLLICLE-STIMULATING-HORMONE; SINGLE-NUCLEOTIDE POLYMORPHISMS; CLASS-II REGION; NONOBSTRUCTIVE AZOOSPERMIA; GENOME-WIDE; PHARMACOGENETIC APPROACH; PROMOTER POLYMORPHISM; VRK1 PHOSPHORYLATES; SUSCEPTIBILITY GENE; FSH RECEPTOR

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