PMID- 35003222 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220111 IS - 1664-8021 (Print) IS - 1664-8021 (Electronic) IS - 1664-8021 (Linking) VI - 12 DP - 2021 TI - Polymorphisms Within DNA Double-Strand Breaks Repair-Related Genes Contribute to Structural Chromosome Abnormality in Recurrent Pregnancy Loss. PG - 787718 LID - 10.3389/fgene.2021.787718 [doi] LID - 787718 AB - 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, p = 0.036 respectively) and controls (OR = 7.130, p = 0.000; OR = 2.157, p = 0.004; OR = 2.397, p = 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 (p = 0.015, 0.012, and 0.007 respectively). Conclusion: 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. CI - Copyright (c) 2021 Cheng, Cheng, Li, Guo, Zhang, Zhang, Liu, Huang and Xu. FAU - Cheng, Zhenbo AU - Cheng Z AD - Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, China. FAU - Cheng, Dehua AU - Cheng D AD - School of Basic Medical Science, Institute of Reproductive and Stem Cell Engineering, Central South University, Changsha, China. AD - Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, China. FAU - Li, Jiancheng AU - Li J AD - Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, China. FAU - Guo, Lihuang AU - Guo L AD - Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, China. FAU - Zhang, Wei AU - Zhang W AD - Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, China. FAU - Zhang, Conghui AU - Zhang C AD - Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, China. FAU - Liu, Yangxu AU - Liu Y AD - Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, China. FAU - Huang, Yue AU - Huang Y AD - Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, China. FAU - Xu, Keqian AU - Xu K AD - Department of Laboratory Medicine, The Third Xiangya Hospital, Central South University, Changsha, China. AD - Department of Laboratory Medicine, Xiangya School of Medicine, Central South University, Changsha, China. LA - eng PT - Journal Article DEP - 20211223 PL - Switzerland TA - Front Genet JT - Frontiers in genetics JID - 101560621 PMC - PMC8733605 OTO - NOTNLM OT - DNA double-strand breaks OT - EP300 OT - gene polymorphisms OT - non-homologous end joining OT - recurrent pregnancy loss OT - structural chromosome abnormalities OT - whole-exome sequencing COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/01/11 06:00 MHDA- 2022/01/11 06:01 PMCR- 2021/12/23 CRDT- 2022/01/10 09:11 PHST- 2021/10/01 00:00 [received] PHST- 2021/12/06 00:00 [accepted] PHST- 2022/01/10 09:11 [entrez] PHST- 2022/01/11 06:00 [pubmed] PHST- 2022/01/11 06:01 [medline] PHST- 2021/12/23 00:00 [pmc-release] AID - 787718 [pii] AID - 10.3389/fgene.2021.787718 [doi] PST - epublish SO - Front Genet. 2021 Dec 23;12:787718. doi: 10.3389/fgene.2021.787718. eCollection 2021.