Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility.
Commun Biol
; 5(1): 1220, 2022 11 10.
Article
in En
| MEDLINE
| ID: mdl-36357561
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-DRß1 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genome-Wide Association Study
/
Infertility, Male
Limits:
Humans
/
Male
Language:
En
Journal:
Commun Biol
Year:
2022
Document type:
Article
Affiliation country:
Spain
Publication country:
ENGLAND
/
ESCOCIA
/
GB
/
GREAT BRITAIN
/
INGLATERRA
/
REINO UNIDO
/
SCOTLAND
/
UK
/
UNITED KINGDOM