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

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

J Perinat Med. 2023 Jul 25;51(8):1082-1096. doi: 10.1515/jpm-2022-0613. Print 2023 Oct 26.

Authors

Ying Chan¹, Xinhua Tang^{1

2}, Dongling Cai³, Yize Liu³, Dongmei Li¹, Jie Su¹, Guowei Neng¹, Yifei Yin¹, Zibiao Geng¹, Shu Zhu¹, Jinman Zhang^{1

2}, Lihong Jiang⁴, Baosheng Zhu^{1

3

2}

Affiliations

¹ 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, Kunming, P.R. China.
² Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan Province, P.R. China.
³ School of Medicine, Kunming University of Science and Technology, Kunming, 650500, Yunnan Province, P.R. China.
⁴ Department of Cardiothoracic Surgery, First People's Hospital of Yunnan Province, 157, Jinbi Road, Kunming, 650032, China.

PMID: 37486214
DOI: 10.1515/jpm-2022-0613

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.