TY - JOUR
T1 - Evaluation of male fertility-associated loci in a european population of patients with severe spermatogenic impairment
AU - Cerván-Martín, Miriam
AU - Bossini-Castillo, Lara
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 - Guzmán-Jiménez, Andrea
AU - Costa, Cláudia
AU - Llinares-Burguet, Inés
AU - Khantham, Chiranan
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
PY - 2021/1
Y1 - 2021/1
N2 - Infertility is a growing concern in developed societies. Two extreme phenotypes of male infertility are non-obstructive azoospermia (NOA) and severe oligospermia (SO), which are characterized by severe spermatogenic failure (SpF). We designed a genetic association study comprising 725 Iberian infertile men as a consequence of SpF and 1058 unaffected controls to evaluate whether five single-nucleotide polymorphisms (SNPs), previously associated with reduced fertility in Hutterites, are also involved in the genetic susceptibility to idiopathic SpF and specific clinical entities. A significant difference in the allele frequencies of USP8-rs7174015 was observed under the recessive model between the NOA group and both the control group (p = 0.0226, OR = 1.33) and the SO group (p = 0.0048, OR = 1.78). Other genetic associations for EPSTI1-rs12870438 and PSAT1-rs7867029 with SO and between TUSC1-rs10966811 and testicular sperm extraction (TESE) success in the context of NOA were observed. In silico analysis of functional annotations demonstrated cis-eQTL effects of such SNPs likely due to the modification of binding motif sites for relevant transcription factors of the spermatogenic process. The findings reported here shed light on the molecular mechanisms leading to severe phenotypes of idiopathic male infertility, and may help to better understand the contribution of the common genetic variation to the development of these conditions.
AB - Infertility is a growing concern in developed societies. Two extreme phenotypes of male infertility are non-obstructive azoospermia (NOA) and severe oligospermia (SO), which are characterized by severe spermatogenic failure (SpF). We designed a genetic association study comprising 725 Iberian infertile men as a consequence of SpF and 1058 unaffected controls to evaluate whether five single-nucleotide polymorphisms (SNPs), previously associated with reduced fertility in Hutterites, are also involved in the genetic susceptibility to idiopathic SpF and specific clinical entities. A significant difference in the allele frequencies of USP8-rs7174015 was observed under the recessive model between the NOA group and both the control group (p = 0.0226, OR = 1.33) and the SO group (p = 0.0048, OR = 1.78). Other genetic associations for EPSTI1-rs12870438 and PSAT1-rs7867029 with SO and between TUSC1-rs10966811 and testicular sperm extraction (TESE) success in the context of NOA were observed. In silico analysis of functional annotations demonstrated cis-eQTL effects of such SNPs likely due to the modification of binding motif sites for relevant transcription factors of the spermatogenic process. The findings reported here shed light on the molecular mechanisms leading to severe phenotypes of idiopathic male infertility, and may help to better understand the contribution of the common genetic variation to the development of these conditions.
KW - Genetic association analysis
KW - Impaired spermatogenesis
KW - Infertility
KW - Non-obstructive azoospermia
KW - Severe oligospermia
KW - SNPs
UR - http://www.scopus.com/inward/record.url?scp=85098882519&partnerID=8YFLogxK
U2 - 10.3390/jpm11010022
DO - 10.3390/jpm11010022
M3 - Article
AN - SCOPUS:85098882519
VL - 11
SP - 1
EP - 19
JO - Journal of Personalized Medicine
JF - Journal of Personalized Medicine
SN - 2075-4426
IS - 1
M1 - 22
ER -