The relationship of maternal polymorphisms of genes related to meiosis and DNA damage repair with fetal chromosomal stability

Ying Chan; Xinhua Tang; Dongling Cai; Yize Liu; Dongmei Li; Jie Su; Guowei Neng; Yifei Yin; Zibiao Geng; Shu Zhu; Jinman Zhang; Lihong Jiang; Baosheng Zhu

doi:10.1515/jpm-2022-0613

Article

The relationship of maternal polymorphisms of genes related to meiosis and DNA damage repair with fetal chromosomal stability

Ying Chan , Xinhua Tang , Dongling Cai , Yize Liu , Dongmei Li , Jie Su , Guowei Neng , Yifei Yin , Zibiao Geng , Shu Zhu , Jinman Zhang , Lihong Jiang and Baosheng Zhu

Published/Copyright: July 25, 2023

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From the journal Journal of Perinatal Medicine Volume 51 Issue 8

Abstract

Objectives

To evaluate the association between maternal polymorphisms of NANOS3 rs2016163, HELQ rs4693089, PRIM1 rs2277339, TLK1 rs10183486, ERCC6 rs2228526, EXO1 rs1635501, DMC1 rs5757133, and MSH5 rs2075789 and fetal chromosomal abnormality.

Methods

This retrospective case-control study included 571 women with fetal chromosome abnormalities (330 pregnant women diagnosed with fetal aneuploidy, 241 with fetal de novo structural chromosome pregnancy) and 811 healthy pregnant women between January 2018 and April 2022. All the above polymorphisms were tested using SNaPshot.

Results

All the eight polymorphisms were analyzed for genotypes, alleles, under dominant and recessive genetic models. Significant distribution differences of TLK1 rs10183486 in fetal chromosome structural abnormality were found between the case group and control subjects who were <35 years of age [Genotype: p=0.029; Dominant: OR (95 %CI)=0.46 (0.25–0.82), p=0.01 and allele: OR (95 %CI)=0.47 (0.27–0.82), p=0.01 respectively], while no difference was found in the recessive model [OR (95 %CI)=2.49 (0.31–20.40), p=0.39]. In advanced age subgroups for fetal aneuploidy, significant differences were found in genotypes analysis of PRIM1 rs2277339 (p=0.008), allele analysis of TLK1 rs10183486 [OR (95 %CI)=0.62 (0.42–0.91), p=0.02]. For the fetal chromosome structural abnormality population, HELQ rs4693089 revealed a significant distribution difference (p=0.01) but not in the allele, dominant and recessive genetic models analysis (p>0.05 individually).

Conclusions

For older women, maternal PRIM1 rs2277339 and TLK1 rs10183486 polymorphisms may be associated with fetal aneuploidy, while HELQ rs4693089 may be associated with fetal chromosome structural abnormality. Also, carriers of T allele of TLK1 rs10183486 have a lower risk of fetal chromosome structural abnormality in younger women.

Keywords: chromosomal de novo structural abnormalities pregnancy; fetal aneuploidy; fetal chromosome stability; gene polymorphism; meiosis and DNA damage repair

Corresponding authors: Lihong Jiang, Department of Cardiothoracic Surgery, The First People’s Hospital of Yunnan Province, 157, Jinbi Road, Kunming, 650032, P.R. China, E-mail: jianglihong_yayy@163.com; and Baosheng Zhu, Department of Medical Genetics, NHC Key Laboratory of Periconception Health Birth in Western China, Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases, The First People’s Hospital of Yunnan Province, 157, Jinbi Road, Kunming, 650032, P.R. China; School of Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan Province, China; and Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan Province, P.R. China, E-mail: bszhu@aliyun.com

Ying Chan and Xinhua Tang contributed equally to this work.

Funding source: Major Scientific and Technological Project of Yunnan Province, Yunnan Provincial Clinical Research Center for Birth Defects and Rare Diseases

Award Identifier / Grant number: 2019ZF015

Funding source: National Natural Science Foundation of China

Award Identifier / Grant number: 82060039

Funding source: Major science and technology projects of Yunnan provincial S&T plan projects

Award Identifier / Grant number: 2018ZF009

Acknowledgment

We thank all participants for their contribution to the study, the colleagues’ assistance for gaining the data analyzed in this study as well as to appreciate the co-workers for their support and guidance. Thank all funds supporting the research and coauthors making their efforts to the manuscript.

Research funding: This study was supported by the grants from the Major science and technology projects of Yunnan provincial S&T plan projects (No.2018ZF009) and Major Scientific and Technological Project of Yunnan Province, Yunnan Provincial Clinical Research Center for Birth Defects and Rare Diseases (No. 2019ZF015); National Natural Science Foundation of China (No. 82060039).
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Conflict of interests: The authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: The study was approved by the Institutional Review Board (KHLL2020-KY025). The study followed the Declaration of Helsinki criteria.
Data availability: The datasets analyzed during the current study are available from the corresponding author upon reasonable request.

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Received: 2022-12-22

Accepted: 2023-06-24

Published Online: 2023-07-25

Published in Print: 2023-10-26

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https://doi.org/10.1515/jpm-2022-0613

Keywords for this article

chromosomal de novo structural abnormalities pregnancy; fetal aneuploidy; fetal chromosome stability; gene polymorphism; meiosis and DNA damage repair