Association of xenobiotic-metabolizing gene cytochrome P450 2E1 variants with preeclampsia in Chinese women

TL;DR

This study finds that specific genetic variants in the CYP2E1 gene are associated with an increased risk of preeclampsia in Chinese women.

Contribution

The study identifies novel associations between CYP2E1 genetic variants and preeclampsia risk in a Chinese population.

Findings

The CYP2E1 C-1054T variant is linked to elevated preeclampsia risk in multiple genetic models.

The TT+CT genotype remains a significant predictor of preeclampsia after adjusting for clinical factors.

Combining C-1054T and 96-bp I/D genotypes further increases preeclampsia risk.

Abstract

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.