TY - JOUR
T1 - Intronic variation of the SOHLH2 gene confers risk to male reproductive impairment
AU - Cerván-Martín, Miriam
AU - Suazo-Sánchez, M. Irene
AU - Rivera-Egea, Rocío
AU - Garrido, Nicolás
AU - Luján, Saturnino
AU - Romeu, Gema
AU - Santos-Ribeiro, Samuel
AU - Castilla, José A.
AU - Gonzalvo, M. Carmen
AU - Clavero, Ana
AU - Vicente, F. Javier
AU - Maldonado, Vicente
AU - Burgos, Miguel
AU - Barrionuevo, Francisco J.
AU - Jiménez, Rafael
AU - Sánchez-Curbelo, Josvany
AU - López-Rodrigo, Olga
AU - Peraza, M. Fernanda
AU - Pereira-Caetano, Iris
AU - Marques, Patricia I.
AU - Carvalho, Filipa
AU - Barros, Alberto
AU - Bassas, Lluís
AU - Seixas, Susana
AU - Gonçalves, João
AU - Larriba, Sara
AU - Lopes, Alexandra M.
AU - Palomino-Morales, Rogelio J.
AU - Carmona, F. David
AU - Calhaz-Jorge, Carlos
AU - Aguiar, Ana
AU - Nunes, Joaquim
AU - Sousa, Sandra
AU - Graça Pinto, Maria
AU - Correia, Sónia
AU - Pacheco, Alberto
AU - González, Cristina
AU - Gómez, Susana
AU - Amorós, David
AU - Aguilar, Jesús
AU - Quintana, Fernando
PY - 2020/8
Y1 - 2020/8
N2 - 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.
AB - 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.
KW - infertility
KW - nonobstructive azoospermia
KW - oligospermia
KW - SOHLH2
KW - spermatogenesis
UR - http://www.scopus.com/inward/record.url?scp=85088150183&partnerID=8YFLogxK
U2 - 10.1016/j.fertnstert.2020.02.115
DO - 10.1016/j.fertnstert.2020.02.115
M3 - Article
C2 - 32690270
AN - SCOPUS:85088150183
SN - 0015-0282
VL - 114
SP - 398
EP - 406
JO - Fertility And Sterility
JF - Fertility And Sterility
IS - 2
ER -