Polymorphisms Within DNA Double-Strand Breaks Repair-Related Genes Contribute to Structural Chromosome Abnormality in Recurrent Pregnancy Loss

作者：Zhenbo Cheng, Dehua Cheng, Jiancheng Li, Lihuang Guo, Wei Zhang, Conghui Zhang, Yangxu Liu, Yue Huang, Keqian Xu · 发表于：Frontiers in Genetics · 年份：2021 · DOI：10.3389/fgene.2021.787718 · 被引用次数：5 · 研究领域：Prenatal Screening and Diagnostics、Reproductive Biology and Fertility、DNA Repair Mechanisms

Background: 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. Methods: 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 ( EP300, XRCC6, LIG4, XRCC4, PRKDC , and DCLRE1C ), 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 in situ hybridization (FISH). Results: A total of 35 polymorphisms have been identified and confirmed. Frequencies of EP300 rs20551, XRCC6 rs132788, and LIG4 rs1805388 were significantly different between SCA RPL and no SCA RPL ( p = 0.030, 0.031, and 0.040 respectively). Frequencies of those three gene polymorphisms between SCA RPL and controls also were significantly different ( p = 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 ( OR = 3.227, p = 0.005; OR = 1.978, p = 0.008 and OR = 1.769,...