Hu Kaifeng, Liu Qingqing, Liu Xinghui, Bai Huai, Wu Yujie, Fan Ping
Laboratory of Genetic Disease and Perinatal Medicine, Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, China.
Reprod Sci. 2025 Jun 11. doi: 10.1007/s43032-025-01890-y.
Environmental and genetic factors are related to the pathogenesis of preeclampsia (PE). Cytochrome P450 2E1 (CYP2E1) is crucial for the metabolism of endogenous and xenobiotic substances, possibly involved in the pathophysiology of PE. This study explored the association between CYP2E1 96-bp insertion/deletion (I/D) and rs2031920 (C-1054T) genetic variants and the risk of PE in 335 patients with PE and 1301 healthy pregnant women. The CYP2E1 C-1054T variant was linked to an elevated risk of PE according to the dominant, genotype, and allele genetic models (P < 0.05). The genotype TT + CT remained a significant predictor of PE in the logistic regression model including age, gestational age, and body mass index at delivery (OR = 1.606, 95% CI: 1.137-2.286; P = 0.007). Moreover, the combined genotype TT + CT/II + ID of the C-1054T and 96-bp I/D variants further heightened the risk of PE, with the combined genotype DD/CC serving as the reference category (OR = 2.383, 95% CI: 1.381-4.106, P = 0.002). Furthermore, patients with the -1054T allele had lower serum albumin levels and total antioxidant capacity, and more severe proteinuria than those with the CC genotype (P < 0.05), and patients with the 96-bp I allele had a relatively higher atherosclerosis index than those with the DD genotype (P = 0.057). No significant differences in genotype frequencies of PE with severe features, platelet count, serum hepatic enzyme activities and creatinine levels were observed according to the different genotypes (P > 0.05). We conclude that the T allele of the C-1054T variant and its integration with the I allele of the 96-bp I/D variant in CYP2E1 are linked to an elevated risk of PE in Chinese women.
环境和遗传因素与子痫前期（PE）的发病机制相关。细胞色素P450 2E1（CYP2E1）对内源性和外源性物质的代谢至关重要，可能参与了PE的病理生理过程。本研究探讨了CYP2E1基因96-bp插入/缺失（I/D）和rs2031920（C-1054T）基因变异与335例PE患者及1301例健康孕妇发生PE风险之间的关联。根据显性、基因型和等位基因遗传模型，CYP2E1 C-1054T变异与PE风险升高相关（P < 0.05）。在包含年龄、孕周和分娩时体重指数的逻辑回归模型中，基因型TT + CT仍是PE的显著预测因子（OR = 1.606，95% CI：1.137 - 2.286；P = 0.007）。此外，C-1054T和96-bp I/D变异的联合基因型TT + CT/II + ID进一步增加了PE风险，以联合基因型DD/CC作为参照类别（OR = 2.383，95% CI：1.381 - 4.106，P = 0.002）。此外，携带-1054T等位基因的患者血清白蛋白水平和总抗氧化能力较低，蛋白尿比CC基因型患者更严重（P < 0.05），携带96-bp I等位基因的患者动脉粥样硬化指数相对高于DD基因型患者（P = 0.057）。根据不同基因型，在PE严重程度、血小板计数、血清肝酶活性和肌酐水平方面未观察到显著差异（P > 0.05）。我们得出结论，CYP2E1基因C-１０５４Ｔ变异的Ｔ等位基因及其与96-bp I/D变异的Ｉ等位基因的整合与中国女性发生PE的风险升高相关。
