Intronic variation of the SOHLH2 gene confers risk to male reproductive impairment
Por:
Cervan-Martin, M, Suazo-Sanchez, MI, Rivera-Egea, R, Garrido, N, Lujan, S, Romeu, G, Santos-Ribeiro, S, Castilla, JA, Gonzalvo, MC, Clavero, A, Vicente, FJ, Maldonado, V, Burgos, M, Barrionuevo, FJ, Jimenez, R, Sanchez-Curbelo, J, Lopez-Rodrigo, O, Peraza, MF, Pereira-Caetano, I, Marques, PI, Carvalho, F, Barros, A, Bassas, L, Seixas, S, Goncalves, J, Larriba, S, Lopes, AM, Palomino-Morales, RJ, Carmona, FD
Publicada:
1 ago 2020
Resumen:
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. ((C) 2020 by American Society for Reproductive Medicine.)
Filiaciones:
Cervan-Martin, M:
Univ Granada, Dept Genet, Granada, Spain
Univ Granada, Inst Biotecnol, Granada, Spain
Inst Invest Biosanitaria Ibs Granada, Granada, Spain
Suazo-Sanchez, MI:
Univ Granada, Dept Genet, Granada, Spain
Univ Granada, Inst Biotecnol, Granada, Spain
Rivera-Egea, R:
IVIRMA Valencia, Androl Lab, Valencia, Spain
IVIRMA Valencia, Sperm Bank, Valencia, Spain
Hlth Res Inst La Fe, IVI Fdn, Valencia, Spain
Garrido, N:
Hlth Res Inst La Fe, IVI Fdn, Valencia, Spain
Hosp Univ & Politecn La Fe, Serv Urol, Valencia, Spain
Inst Invest Sanitaria La Fe, Valencia, Spain
Lujan, S:
Univ Porto I3S, Inst Invest & Inovaco Saude, Porto, Portugal
Romeu, G:
Hosp Univ & Politecn La Fe, Serv Urol, Valencia, Spain
Inst Invest Sanitaria La Fe, Valencia, Spain
Santos-Ribeiro, S:
Hosp Univ & Politecn La Fe, Serv Urol, Valencia, Spain
Inst Invest Sanitaria La Fe, Valencia, Spain
IVI RMA Lisbon, Lisbon, Portugal
Univ Lisbon, Dept Obstet & Gynecol, Fac Med, Lisbon, Portugal
Castilla, JA:
Inst Invest Biosanitaria Ibs Granada, Granada, Spain
HU Virgen de las Nieves, UGC Obstet & Ginecol, Unidad Reprod, Granada, Spain
CEIFER Biobanco NextClin, Granada, Spain
Gonzalvo, MC:
Inst Invest Biosanitaria Ibs Granada, Granada, Spain
HU Virgen de las Nieves, UGC Obstet & Ginecol, Unidad Reprod, Granada, Spain
Clavero, A:
Inst Invest Biosanitaria Ibs Granada, Granada, Spain
HU Virgen de las Nieves, UGC Obstet & Ginecol, Unidad Reprod, Granada, Spain
Vicente, FJ:
Inst Invest Biosanitaria Ibs Granada, Granada, Spain
HU Virgen de las Nieves, UGC Urol, Granada, Spain
Maldonado, V:
Complejo Hosp Jaen, UGC Obstet & Ginecol, Jaen, Spain
Burgos, M:
Univ Granada, Dept Genet, Granada, Spain
Univ Granada, Inst Biotecnol, Granada, Spain
Barrionuevo, FJ:
Univ Granada, Dept Genet, Granada, Spain
Univ Granada, Inst Biotecnol, Granada, Spain
Jimenez, R:
Univ Granada, Dept Genet, Granada, Spain
Univ Granada, Inst Biotecnol, Granada, Spain
Sanchez-Curbelo, J:
Androl Serv Fundacio Puigvert, Lab Seminol & Embryol, Barcelona, Spain
Lopez-Rodrigo, O:
Androl Serv Fundacio Puigvert, Lab Seminol & Embryol, Barcelona, Spain
Peraza, MF:
Androl Serv Fundacio Puigvert, Lab Seminol & Embryol, Barcelona, Spain
Pereira-Caetano, I:
Inst Nacl Saude Dr Ricardo Jorge, Dept Genet Humana, Lisbon, Portugal
Marques, PI:
Univ Porto I3S, Inst Invest & Inovaco Saude, Porto, Portugal
Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, Porto, Portugal
Bellvitge Biomed Res Inst IDIBELL, Human Mol Genet Grp, Barcelona, Spain
Univ Granada, Dept Bioquim & Biol Mol, Granada, Spain
Carvalho, F:
Nova Med Sch, ToxOm Ctr Toxicogen & Saude Humana, Lisbon, Portugal
Barros, A:
Nova Med Sch, ToxOm Ctr Toxicogen & Saude Humana, Lisbon, Portugal
Bassas, L:
Androl Serv Fundacio Puigvert, Lab Seminol & Embryol, Barcelona, Spain
Seixas, S:
Univ Porto I3S, Inst Invest & Inovaco Saude, Porto, Portugal
Bellvitge Biomed Res Inst IDIBELL, Human Mol Genet Grp, Barcelona, Spain
Univ Granada, Dept Bioquim & Biol Mol, Granada, Spain
Goncalves, J:
Inst Nacl Saude Dr Ricardo Jorge, Dept Genet Humana, Lisbon, Portugal
Univ Porto I3S, Inst Invest & Inovaco Saude, Porto, Portugal
Larriba, S:
Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, Porto, Portugal
Lopes, AM:
Univ Porto I3S, Inst Invest & Inovaco Saude, Porto, Portugal
Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, Porto, Portugal
Bellvitge Biomed Res Inst IDIBELL, Human Mol Genet Grp, Barcelona, Spain
Univ Granada, Dept Bioquim & Biol Mol, Granada, Spain
Palomino-Morales, RJ:
Inst Invest Biosanitaria Ibs Granada, Granada, Spain
Univ Porto, Fac Med, Dept Pathol, Serv Genet, Porto, Portugal
Carmona, FD:
Univ Granada, Dept Genet, Granada, Spain
Univ Granada, Inst Biotecnol, Granada, Spain
Inst Invest Biosanitaria Ibs Granada, Granada, Spain
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