He Linbin, Wang Lijuan, Gong Ziqiang, Li Ziye, Xia Fan, Wang Peiwen, Guo Suyan, Lin Shanyu, Chen Lizhang, Wang Tingting
Department of Epidemiology and Health Statistics, Xiangya School of Public Health, Central South University, 110 Xiangya Road, Changsha, 410078, Hunan, China.
Hunan Provincial Maternal and Child Health Care Hospital, No.53, Xiangchun Road, Kaifu District, Changsha, 410008, Hunan, China.
Reprod Sci. 2025 Jun 16. doi: 10.1007/s43032-025-01892-w.
This study aimed to evaluate the association of THBS1 (Thrombospondin 1) and P21 gene polymorphisms and their interaction with the risk of PE. A case-control study was conducted, involving 175 pregnant women with PE and 350 normotensive pregnant women recruited from two tertiary hospitals. Genotyping of 13 single-nucleotide polymorphisms in the THBS1 and P21 genes was performed using the MassArray platform. Univariate and multivariate logistic regression analyses were performed to evaluate the association between THBS1 and P21 gene polymorphisms and risk of PE. Classification and regression tree (CART) analysis was used to identify potential gene-gene interactions, and logistic regression was applied to assess their impact on PE risk. After adjusting for confounding factors, the THBS1 rs2169830 polymorphism was significantly associated with decreased susceptibility to PE (additive model: aOR = 0.12, p = 0.003), while the P21 rs762624 polymorphism was significantly associated with an increased risk of PE (additive model: aOR = 2.24, p = 0.002). CART and logistic regression analyses identified a significant effect of interaction between polymorphisms in rs762624, rs2292305, and rs1478604 on the susceptibility of PE, with individuals carrying the rs762624CC-rs2292305AA/GG-rs1478604TT/CC genotype combination having the highest risk of PE (aOR = 4.533, p < 0.001). Our findings highlight the importance of THBS1 rs2169830 and P21 rs762624 polymorphisms, along with their interaction, in influencing PE risk. The present study provides a foundation for a more profound understanding of the mechanisms underlying PE.
本研究旨在评估血小板反应蛋白1（THBS1）和P21基因多态性的关联及其与子痫前期风险的相互作用。开展了一项病例对照研究，纳入了从两家三级医院招募的175例子痫前期孕妇和350例血压正常的孕妇。使用MassArray平台对THBS1和P21基因中的13个单核苷酸多态性进行基因分型。进行单因素和多因素逻辑回归分析，以评估THBS1和P21基因多态性与子痫前期风险之间的关联。采用分类回归树（CART）分析来识别潜在的基因-基因相互作用，并应用逻辑回归评估其对子痫前期风险的影响。在调整混杂因素后，THBS1 rs2169830多态性与子痫前期易感性降低显著相关（相加模型：调整后比值比[aOR]=0.12，p=0.003），而P21 rs762624多态性与子痫前期风险增加显著相关（相加模型：aOR=2.24，p=0.002）。CART和逻辑回归分析确定，rs762624、rs2292305和rs1478604多态性之间的相互作用对子痫前期易感性有显著影响，携带rs762624CC-rs2292305AA/GG-rs1478604TT/CC基因型组合的个体患子痫前期的风险最高（aOR=4.533，p<0.001）。我们的研究结果突出了THBS1 rs2169830和P21 rs762624多态性及其相互作用在影响子痫前期风险方面的重要性。本研究为更深入了解子痫前期潜在机制奠定了基础。
