Department of Medical Genetics, NHC Key Laboratory of Periconception Health Birth in Western China, Yunnan Provincial Key Laboratory for Birth Defects and Genetic Diseases, First People's Hospital of Yunnan Province, 157, Jinbi Road, Kunming, 650032, China.
Medical Faculty & Affiliated Hospital, Kunming University of Science and Technology, Kunming, Yunnan Province, 650500, China.
BMC Pregnancy Childbirth. 2023 Aug 30;23(1):624. doi: 10.1186/s12884-023-05945-3.
Aneuploidy pregnancy is a severe major birth defect and causes about 50% spontaneous miscarriages with unknown etiology. To date, only a few epidemiological studies with small sample sizes have investigated the risk factors for aneuploidy pregnancy. TP53, MDM2, and miR-34b/c genes are implicated in tumorigenesis with aneuploidy, yet the function of their polymorphisms in aneuploidy pregnancy susceptibility needs to be clarified.
To elucidate the association of TP53 rs1042522 G > C, MDM2 rs2279744 309 T > G, and miR-34b/c rs4938723 T > C specific polymorphisms with aneuploidy pregnancy.
In the retrospective case-control study, 330 aneuploidies pregnancy women and 813 normal pregnancy controls were recruited between January 2018 and April 2022 at the First People's Hospital of Yunnan Province, Kunming, China. Three functional polymorphisms, the TP53 rs1042522 G > C (Arg72Pro), MDM2 rs2279744 309 T > G, and miR-34b/c rs4938723 T > C, were genotyped using the snapshot method.
The frequency distribution of three genotypic variants was not different between case and control pregnant women and was similar to with Hardy-Weinberg Equilibrium (HWE). However, in the younger subgroup (less than 35 years old), a significant difference was detected in allele and recessive model (p = 0.01). In the advanced age subgroup (more than or equal to 35 years old), G of MDM2 rs2279744 T > G revealed a significantly higher frequency in cases than controls (p = 0.045), and miR-34b/c rs4938723 T > C revealed a significant difference under the dominant model (p = 0.03), but no significant differences were observed in other models and in both younger and older subgroup (p > 0.05, respectively). These results suggest that individual polymorphisms were not associated with aneuploidy pregnancy, combined with age, they may serve as a risk factor for aneuploidy pregnancy.
Combination of TP53 rs1042522 G > C, MDM2 rs2279744 T > G, and miR-34b/c rs4938723 T > C polymorphisms with maternal age may be related to aneuploidy pregnancy susceptibility. These findings might elaborate on the genetic etiology of aneuploidy pregnancy.
非整倍体妊娠是一种严重的主要出生缺陷，约 50%的非整倍体妊娠会自发流产，其病因不明。迄今为止，只有少数样本量较小的流行病学研究调查了非整倍体妊娠的危险因素。TP53、MDM2 和 miR-34b/c 基因与非整倍体肿瘤的发生有关，但其多态性与非整倍体妊娠易感性的关系尚需阐明。
阐明 TP53 rs1042522 G> C、MDM2 rs2279744 309 T>G 和 miR-34b/c rs4938723 T>C 特异性多态性与非整倍体妊娠的关系。
在回顾性病例对照研究中，于 2018 年 1 月至 2022 年 4 月在云南省第一人民医院招募了 330 例非整倍体妊娠妇女和 813 例正常妊娠对照。采用快照法检测 TP53 rs1042522 G>C（Arg72Pro）、MDM2 rs2279744 309 T>G 和 miR-34b/c rs4938723 T>C 三种功能多态性。
病例组和对照组孕妇三种基因型的频率分布与 Hardy-Weinberg 平衡（HWE）无差异，但在年轻亚组（<35 岁），等位基因和隐性模型存在显著差异（p=0.01）。在高龄亚组（≥35 岁），MDM2 rs2279744 T>G 的 G 等位基因在病例组中的频率明显高于对照组（p=0.045），miR-34b/c rs4938723 T>C 在显性模型下存在显著差异（p=0.03），但其他模型及年轻和高龄亚组均无差异（p>0.05）。这些结果表明，个体多态性与非整倍体妊娠无关，与年龄结合，可能成为非整倍体妊娠的危险因素。
TP53 rs1042522 G>C、MDM2 rs2279744 T>G 和 miR-34b/c rs4938723 T>C 多态性与母体年龄的组合可能与非整倍体妊娠易感性有关。这些发现可能阐明了非整倍体妊娠的遗传病因。
