DEFB126 polymorphisms and association with idiopathic asthenozoospermia in China
Jiao-Yu He1,2, Jian-Ying Peng1,2, Qiu-Fu Li1,2, Xiao-Li Lin1,2, Yan-Ru Cui1,2, Shi-Yu Ma1,2, Shi-Yun Fan1,2, Yi-Ran Liu1,2, Zhi-Lin Song1,2, Jun-Hang Deng1,2, Xia Wei1,2, Xian-Ping Ding1,2
1 Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China
2 Chongqing Nanchuan Biotechnology Research Institute, Bio-resource Research and Utilization Joint Key Laboratory of Sichuan and Chongqing, Chongqing 400000, China
Key Laboratory of Bio-Resources and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065; Chongqing Nanchuan Biotechnology Research Institute, Bio-resource Research and Utilization Joint Key Laboratory of Sichuan and Chongqing, Chongqing 400000
Source of Support: None, Conflict of Interest: None
Idiopathic asthenozoospermia, a common factor in male infertility, is characterized by altered sperm motility function in fresh ejaculate. Although the β-defensin 126 (DEFB126) protein is associated with asthenozoospermia, DEFB126 gene polymorphisms have not been extensively studied. Therefore, the association between DEFB126 gene polymorphisms and asthenozoospermia requires further investigation. Screening was performed by semen analysis, karyotype analysis, and Y microdeletion detection, and 102 fertile men and 106 men with asthenozoospermia in Chengdu, China, were selected for DEFB126 gene sequence analyses. Seven nucleotide mutations and two nucleotide deletions in the DEFB126 gene were detected. rs11467417 (317–318 del/del), rs11467497 (163–166 wt/del), c.152T>C, and c.227A>G were significantly different between the control and asthenozoospermia groups, likely representing high-risk genetic factors for asthenozoospermia among males. DEFB126 expression was not observed in sperm with rs11467497 homozygous deletion and was unstable in sperm with rs11467417 homozygous deletion. The rs11467497 four-nucleotide deletion leads to truncation of DEFB126 at the carboxy-terminus, and the rs11467417 binucleotide deletion produces a non-stop messenger RNA (mRNA). The above deletions may be responsible for male hypofertility and infertility by reducing DEFB126 affinity to sperm surfaces. Based on in silico analysis, the amino acids 51M and 76K are located in the highly conserved domain; c.152T>C (M51T) and c.227A>G (K76R) are predicted to be damaging and capable of changing alternative splice, structural and posttranslational modification sites of the RNA, as well as the secondary structure, structural stability, and hydrophobicity of the protein, suggesting that these mutations are associated with asthenozoospermia.