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

被引：10

作者：

Cervan-Martin, Miriam ^{[1
,2
,3
]}

Tuettelmann, Frank ^{[4
]}

Lopes, Alexandra M. ^{[5
,6
,7
]}

Bossini-Castillo, Lara ^{[1
,2
,3
]}

Rivera-Egea, Rocio ^{[8
,9
,10
]}

Garrido, Nicolas ^{[10
,11
,12
]}

Lujan, Saturnino ^{[11
,12
]}

Romeu, Gema ^{[11
,12
]}

Santos-Ribeiro, Samuel ^{[13
,14
]}

Castilla, Jose A. ^{[3
,15
,16
]}

Carmen Gonzalvo, M. ^{[3
,15
]}

Clavero, Ana ^{[3
,15
]}

Maldonado, Vicente ^{[17
]}

Vicente, F. Javier ^{[3
,18
]}

Gonzalez-Munoz, Sara ^{[1
,2
,3
]}

Guzman-Jimenez, Andrea ^{[1
,2
,3
]}

Burgos, Miguel ^{[1
,2
]}

Jimenez, Rafael ^{[1
,2
]}

Pacheco, Alberto ^{[10
,19
]}

Gonzalez, Cristina ^{[10
]}

Gomez, Susana ^{[10
]}

Amoros, David ^{[10
]}

Aguilar, Jesus ^{[10
]}

Quintana, Fernando ^{[10
]}

Calhaz-Jorge, Carlos ^{[20
]}

Aguiar, Ana ^{[20
]}

Nunes, Joaquim ^{[20
]}

Sousa, Sandra ^{[20
]}

Pereira, Isabel ^{[20
]}

Pinto, Maria Graca ^{[21
]}

Correia, Sonia ^{[21
]}

Sanchez-Curbelo, Josvany ^{[22
]}

Lopez-Rodrigo, Olga ^{[22
]}

Martin, Javier ^{[23
]}

Pereira-Caetano, Iris ^{[24
]}

Marques, Patricia I. ^{[5
,6
]}

Carvalho, Filipa ^{[5
,25
]}

Barros, Alberto ^{[5
,25
]}

Gromoll, Joerg ^{[26
]}

Bassas, Lluis ^{[22
]}

Seixas, Susana ^{[5
,6
]}

Goncalves, Joao ^{[24
,27
]}

Larriba, Sara ^{[28
]}

Kliesch, Sabine ^{[29
]}

Palomino-Morales, Rogelio J. ^{[3
,30
]}

Carmona, F. David ^{[1
,2
,3
]}

机构：

[1] Univ Granada, Ctr Invest Biomed CIBM, Dept Genet, Granada, Spain

[2] Univ Granada, Ctr Invest Biomed CIBM, Inst Biotecnol, Granada, Spain

[3] Inst Invest Biosanitaria Ibs Granada, Granada, Spain

[4] Univ Munster, Inst Reprod Genet, Munster, Germany

[5] Univ Porto I3S, Inst Invest & Inovacao Saude, Porto, Portugal

[6] Univ Porto IPATIMUP, Inst Mol Pathol & Immunol, Porto, Portugal

[7] Univ Porto, Inst Cell & Mol Biol, Ctr Predict & Prevent Genet, Porto, Portugal

[8] IVI RMA Valencia, Androl Lab, Valencia, Spain

[9] IVI RMA Valencia, Sperm Bank, Valencia, Spain

[10] IVI Fdn, Hlth Res Inst La Fe, Valencia, Spain

[11] Hosp Univ & Politecn La Fe, Serv Urol, Valencia, Spain

[12] Inst Invest Sanitaria La Fe IIS La Fe, Valencia, Spain

[13] IVI RMA Lisbon, Lisbon, Portugal

[14] Univ Lisbon, Fac Med, Dept Obstet & Gynecol, Lisbon, Portugal

[15] HU Virgen de las Nieves, Unidad Reprod, UGC Obstet & Ginecol, Granada, Spain

[16] CEIFER Biobanco GAMETIA, Granada, Spain

[17] Complejo Hosp Jaen, UGC Obstet & Ginecol, Jaen, Spain

[18] HU Virgen de las Nieves, UGC Urol, Granada, Spain

[19] Univ Alfonso X El Sabio, Fac CC Salud, Madrid, Spain

[20] Ctr Hosp Univ Lisboa Norte, Hosp Santa Maria, Unidade Med Reprod, Dept Obstet Ginecol & Med Reprod, Lisbon, Portugal

[21] Ctr Hosp Univ Lisboa Cent, Ctr Med Reprod, Maternidade Dr Alfredo Costa, Lisbon, Portugal

[22] Fundacio Puigvert, Androl Serv, Lab Seminol & Embryol, Barcelona, Spain

[23] PTS Granada, IPBLN CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada, Spain

[24] Inst Nacl Saude Dr Ricardo Jorge, Dept Genet Humana, Lisbon, Portugal

[25] Univ Porto, Fac Med, Dept Patol, Serv Genet, Porto, Portugal

[26] Univ Munster, Inst Reprod & Regenerat Biol, Ctr Reprod Med & Androl, Univ Clin, Munster, Germany

[27] Nova Med Sch, ToxOm Ctr Toxicogenom & Saude Humana, Lisbon, Portugal

[28] Hosp Llobregat, Human Mol Genet Grp, Bellvitge Biomed Res Inst IDIBELL, Barcelona, Spain

[29] Univ Hosp Munster, Ctr Reprod Med & Androl, Dept Clin & Surg Androl, Munster, Germany

[30] Univ Granada, Dept Bioquim & Biol Mol 1, Granada, Spain

来源：

COMMUNICATIONS BIOLOGY | 2022年 / 5卷 / 01期

关键词：

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

D O I：

10.1038/s42003-022-04192-0

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：13

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