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 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

Reparación de la insuficiencia mitral funcional mediante abordaje del aparato subvalvular. Resultados a medio plazo

Introducción y objetivos: El tratamiento quirúrgico de la insuficiencia mitral funcional continúa siendo objeto de amplio debate dada su elevada morbimortalidad y la ausencia de consenso acerca de la mejor opción terapéutica (reparación vs. sustitución). Presentamos nuestra experiencia a medio plazo en su tratamiento mediante reparación valvular con abordaje del aparato subvalvular. Métodos: Entre los años 2012 y 2016 se intervino en nuestro centro a un total de 16 pacientes con insuficiencia mitral de mecanismo iiib de Carpentier con un EuroSCORE logístico medio del 10,81%. En todos ellos se llevó a cabo una anuloplastia mitral restrictiva, junto con reposicionamiento del músculo papilar posteromedial en 14 casos y reaproximación de los músculos papilares en 2 casos. En 12 pacientes se llevó a cabo otro procedimiento asociado. Resultados: El tiempo de seguimiento medio fue de 29,5 meses. Hubo 2 muertes perioperatorias. No hubo más fallecimientos durante el seguimiento. La recurrencia de insuficiencia mitral > 2 fue del 12,5% (2 pacientes). Únicamente los 2 pacientes con insuficiencia mitral > 2 reingresaron en algún momento del seguimiento por insuficiencia cardíaca, permaneciendo el resto en clase funcional i-ii/iv. Conclusiones: El abordaje del aparato subvalvular en la reparación de la insuficiencia mitral funcional se presenta como una alternativa válida en el tratamiento de este tipo de insuficiencia, ofreciendo buenos resultados en lo que a evolución postoperatoria y tasa de recidiva a medio plazo se refiere

Intronic variation of the SOHLH2 gene confers risk to male reproductive impairment

Objective: To evaluate whether SOHLH2 intronic variation contributes to the genetic predisposition to male infertility traits, including severe oligospermia (SO) and different nonobstructive azoospermia (NOA) clinical phenotypes. Design: Genetic association study. Setting: Not applicable. Patient(s): Five hundred five cases (455 infertile patients diagnosed with NOA and 50 with SO) and 1,050 healthy controls from Spain and Portugal. Intervention(s): None. Main outcome measure(s): Genomic DNA extraction from peripheral blood mononuclear cells, genotyping of the SOHLH2 polymorphisms rs1328626 and rs6563386 using the TaqMan allelic discrimination technology, case-control association analyses using logistic regression models, and exploration of functional annotations in publicly available databases. Result(s): Evidence of association was observed for both rs6563386 with SO and rs1328626 with unsuccessful sperm retrieval after testicular sperm extraction (TESE-) in the context of NOA. A dominant effect of the minor alleles was suggested in both associations, either when the subset of patients with the manifestation were compared against the control group (rs6563386/SO: P=.021, odds ratio [OR] = 0.51; rs1328626/TESE-: P=.066, OR = 1.46) or against the group of patients without the manifestation (rs6563386/SO: P=.014, OR = 0.46; rs1328626/TESE-: P=.012, OR = 2.43). The haplotype tests suggested a combined effect of both polymorphisms. In silico analyses evidenced that this effect could be due to alteration of the isoform population. Conclusion(s): Our data suggest that intronic variation of SOHLH2 is associated with spermatogenic failure. The genetic effect is likely caused by different haplotypes of rs6563386 and rs1328626, which may predispose to SO or TESE- depending on the specific allelic combination.info:eu-repo/semantics/publishedVersio