RT Journal Article
T1 Common genetic variation in KATNAL1 non-coding regions is involved in the susceptibility to severe phenotypes of male infertility.
A1 Cerván-Martín, Miriam
A1 Bossini-Castillo, Lara
A1 Guzmán-Jiménez, Andrea
A1 Rivera-Egea, Rocío
A1 Garrido, Nicolás
A1 Lujan, Saturnino
A1 Romeu, Gema
A1 Santos-Ribeiro, Samuel
A1 IVIRMA Group, 
A1 Lisbon Clinical Group, 
A1 Castilla, José Antonio
A1 Gonzalvo, María Del Carmen
A1 Clavero, Ana
A1 Maldonado, Vicente
A1 Vicente, Francisco Javier
A1 Burgos, Miguel
A1 Jiménez, Rafael
A1 González-Muñoz, Sara
A1 Sánchez-Curbelo, Josvany
A1 López-Rodrigo, Olga
A1 Pereira-Caetano, Iris
A1 Marques, Patricia Isabel
A1 Carvalho, Filipa
A1 Barros, Alberto
A1 Bassas, Lluís
A1 Seixas, Susana
A1 Gonçalves, João
A1 Larriba, Sara
A1 Lopes, Alexandra Manuel
A1 Palomino-Morales, Rogelio Jesús
A1 Carmona, Francisco David
K1 KATNAL1
K1 SNP
K1 male infertility
K1 spermatogenesis
K1 splicing
AB Previous studies in animal models evidenced that genetic mutations of KATNAL1, resulting in dysfunction of its encoded protein, lead to male infertility through disruption of microtubule remodelling and premature germ cell exfoliation. Subsequent studies in humans also suggested a possible role of KATNAL1 single-nucleotide polymorphisms in the development of male infertility as a consequence of severe spermatogenic failure. The main objective of the present study is to evaluate the effect of the common genetic variation of KATNAL1 in a large and phenotypically well-characterised cohort of infertile men because of severe spermatogenic failure. A total of 715 infertile men because of severe spermatogenic failure, including 210 severe oligospermia and 505 non-obstructive azoospermia patients, as well as 1058 unaffected controls were genotyped for three KATNAL1 single-nucleotide polymorphism taggers (rs2077011, rs7338931 and rs2149971). Case-control association analyses by logistic regression assuming different models and in silico functional characterisation of risk variants were conducted. Genetic associations were observed between the three analysed taggers and different severe spermatogenic failure groups. However, in all cases, the haplotype model (rs2077011*C | rs7338931*T | rs2149971*A) better explained the observed associations than the three risk alleles independently. This haplotype was associated with non-obstructive azoospermia (adjusted p = 4.96E-02, odds ratio = 2.97), Sertoli-cell only syndrome (adjusted p = 2.83E-02, odds ratio = 5.16) and testicular sperm extraction unsuccessful outcomes (adjusted p = 8.99E-04, odds ratio = 6.13). The in silico analyses indicated that the effect on severe spermatogenic failure predisposition could be because of an alteration of the KATNAL1 splicing pattern. Specific allelic combinations of KATNAL1 genetic polymorphisms may confer a risk of developing severe male infertility phenotypes by favouring the overrepresentation of a short non-functional transcript isoform in the testis.
YR 2022
FD 2022-07-08
LK http://hdl.handle.net/10668/19906
UL http://hdl.handle.net/10668/19906
LA en
DS RISalud
RD Apr 10, 2025