Xi Qi, Zhang Hao, Zhang Xinyue, Jiang Yuting, Wang Ruixue, Liu Ruizhi, Zhang Hongguo
Center for Reproductive Medicine and Center for Prenatal Diagnosis, First Hospital, Jilin University, Changchun.
Center for Reproductive Medicine, Yanbian University Hospital, Yanji, China.
Medicine (Baltimore). 2020 Jun 5;99(23):e20561. doi: 10.1097/MD.0000000000020561.
Nonobstructive azoospermia (NOA) is a severe form of male infertility. The molecular basis of NOA is still poorly understood. The aim of this study was to explore the associations between single nucleotide polymorphisms (SNPs) of the TATA-box binding protein associated factor 4b (TAF4B) gene and NOA. A total of 100 Han Chinese patients with NOA and 100 healthy men as controls were recruited. Targeted gene capture sequencing was performed. A total of 11 TAF4B SNPs were screened in the NOA and control subjects. Six synonymous and 4 nonsynonymous variants were detected. The c.11G>T (p.G4V) mutation was detected only in NOA patients. Polymorphism Phenotyping v2 and Sorting Intolerant From Tolerant analysis indicated that the p.G4V mutation influenced the protein structure of TAF4B. Haplotype analysis showed that the candidate SNPs did not independently associate with NOA and were found at extremely low frequencies in the subject population. Mutation Taster analysis indicated that the c.11G>T/p.G4V mutation was damaging. WebLogo analysis showed that the residue at amino acid 4 was relatively conserved. The p.Gly4Val substitution may affect the structure of the TAF4B protein. The c.11G>T mutation of the TAF4B gene may be associated with NOA in a Chinese population. Bioinformatics analysis indicated this variation may play an important role in the process of spermatogenesis.
非梗阻性无精子症(NOA)是男性不育的一种严重形式。目前对NOA的分子基础仍知之甚少。本研究旨在探讨TATA盒结合蛋白相关因子4b(TAF4B)基因的单核苷酸多态性(SNP)与NOA之间的关联。共招募了100例汉族NOA患者和100例健康男性作为对照。进行了靶向基因捕获测序。在NOA患者和对照者中总共筛选出11个TAF4B SNP。检测到6个同义变异和4个非同义变异。仅在NOA患者中检测到c.11G>T(p.G4V)突变。多态性表型分析v2和从耐受中筛选不耐受分析表明,p.G4V突变影响了TAF4B的蛋白质结构。单倍型分析表明,候选SNP与NOA无独立关联,且在研究人群中出现频率极低。突变预测分析表明,c.11G>T/p.G4V突变具有损害性。WebLogo分析表明,第4位氨基酸残基相对保守。p.Gly4Val替换可能会影响TAF4B蛋白的结构。TAF4B基因的c.11G>T突变可能与中国人群的NOA有关。生物信息学分析表明,这种变异可能在精子发生过程中起重要作用。