Cheng Zhenbo, Cheng Dehua, Li Jiancheng, Guo Lihuang, Zhang Wei, Zhang Conghui, Liu Yangxu, Huang Yue, Xu Keqian
Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, China.
Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, China.
Front Genet. 2021 Dec 23;12:787718. doi: 10.3389/fgene.2021.787718. eCollection 2021.
Structural chromosome abnormality (SCA) is an important cause of human diseases, including recurrent pregnancy loss (RPL). DNA double-strand breaks (DSBs) repair-related genes play critical roles in SCA. The present study aims to investigate the potential contribution of DSBs repair-related gene polymorphisms to SCA. Fifty-four affected RPL individuals with SCA, 88 affected RPL individuals without SCA, and 84 controls were analyzed. Targeted whole-exome sequencing (WES) was used for screening single nucleotide polymorphisms in six DSBs repair-related genes (, and ), and validation was performed by Sanger sequencing. Finally, we detected the frequency of radiation-induced chromosome translocations in no SCA samples with significant polymorphisms by fluorescence hybridization (FISH). A total of 35 polymorphisms have been identified and confirmed. Frequencies of rs20551, rs132788, and rs1805388 were significantly different between SCA RPL and no SCA RPL ( = 0.030, 0.031, and 0.040 respectively). Frequencies of those three gene polymorphisms between SCA RPL and controls also were significantly different ( = 0.017, 0.028, and 0.029 respectively). Moreover, the frequency of the G allele at rs20551 locus, the T allele at rs132788 locus and the A allele at rs1805388 locus was significantly higher in SCA RPL than no SCA RPL ( = 3.227, = 0.005; = 1.978, = 0.008 and = 1.769, = 0.036 respectively) and controls ( = 7.130, = 0.000; = 2.157, = 0.004; = 2.397, = 0.003 respectively). Additionally, the frequency of radiation-induced translocation in no SCA samples with rs20551, rs132788 or rs1805388 was significantly higher compared with the wild type samples ( = 0.015, 0.012, and 0.007 respectively). Our results suggest that rs20551, rs132788, and rs1805388 might be associated with the risk of SCA. Larger scales of genetic variations studies and functional experiments are necessary to further confirm these findings.
染色体结构异常（SCA）是包括复发性流产（RPL）在内的人类疾病的重要病因。DNA双链断裂（DSB）修复相关基因在SCA中起关键作用。本研究旨在探讨DSB修复相关基因多态性对SCA的潜在影响。分析了54例患有SCA的RPL患者、88例未患SCA的RPL患者和84名对照。采用靶向全外显子组测序（WES）筛选6个DSB修复相关基因（……）中的单核苷酸多态性，并通过桑格测序进行验证。最后，我们通过荧光原位杂交（FISH）检测了具有显著多态性的无SCA样本中辐射诱导的染色体易位频率。共鉴定并确认了35个多态性。rs20551、rs132788和rs1805388在SCA-RPL组与无SCA-RPL组之间的频率差异显著（分别为P = 0.030、0.031和0.040）。这三个基因多态性在SCA-RPL组与对照组之间的频率也存在显著差异（分别为P = 0.017、0.028和0.029）。此外，rs20551位点的G等位基因、rs132788位点的T等位基因和rs1805388位点的A等位基因在SCA-RPL组中的频率显著高于无SCA-RPL组（分别为OR = 3.227，P = 0.005；OR = 1.978，P = 0.008；OR = 1.769，P = 0.036）和对照组（分别为OR = 7.130，P = 0.000；OR = 2.157，P = 0.004；OR = 2.397，P = 0.003）。此外，具有rs20551、rs132788或rs1805388的无SCA样本中辐射诱导易位的频率显著高于野生型样本（分别为P = 0.015、0.012和0.007）。我们的结果表明，rs20551、rs132788和rs1805388可能与SCA风险相关。需要更大规模的遗传变异研究和功能实验来进一步证实这些发现。
