Modulation of CYP2E1 metabolic activity in a cohort of confirmed caffeine ingesting pregnant women with preterm offspring.

IF 2.4 Q1 PEDIATRICS Molecular and cellular pediatrics Pub Date : 2020-06-01 DOI:10.1186/s40348-020-00096-3
M R Alcorta-García, C N López-Villaseñor, G Sánchez-Ferrer, H Flores-Mendoza, F Castorena-Torres, M A Aguilar-Torres, C M Sepúlveda-Treviño, J A Hernández-Hernández, R C López-Sánchez, V J Lara-Díaz
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Abstract

Background: To ascertain interactions of caffeine ingestion, food, medications, and environmental exposures during preterm human gestation, under informed consent, we studied a cohort of Mexican women with further preterm offspring born at ≤ 34 completed weeks. At birth, blood samples were taken from mothers and umbilical cords to determine caffeine and metabolites concentrations and CYP1A2 (rs762551) and CYP2E1 (rs2031920, rs3813867) polymorphisms involved in caffeine metabolism.

Results: In 90 pregnant women who gave birth to 98 preterm neonates, self-informed caffeine ingestion rate was 97%, laboratory confirmed rate was 93 %. Theobromine was the predominant metabolite found. Consumption of acetaminophen correlated significantly with changes in caffeine metabolism (acetaminophen R2 = 0.637, p = 0.01) due to activation of CYP2E1 alternate pathways. The main caffeine source was cola soft drinks.

Conclusion: Environmental exposures, especially acetaminophen ingestion during human preterm pregnancy, can modulate CYP2E1 metabolic activity.

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CYP2E1代谢活性的调节在证实咖啡因摄入的早产孕妇队列中。
背景:为了确定咖啡因摄入、食物、药物和环境暴露在人类早产妊娠期间的相互作用,在知情同意的情况下,我们研究了一组墨西哥妇女,她们的后代在≤34周出生。出生时,从母亲和脐带采集血液样本,以确定咖啡因和代谢物浓度以及参与咖啡因代谢的CYP1A2 (rs762551)和CYP2E1 (rs2031920, rs3813867)多态性。结果:90例分娩98例早产儿的孕妇中,自知咖啡因摄入率为97%,实验室确证率为93%。可可碱是主要代谢物。由于CYP2E1替代通路的激活,对乙酰氨基酚的摄入与咖啡因代谢的变化显著相关(对乙酰氨基酚R2 = 0.637, p = 0.01)。主要的咖啡因来源是可乐软饮料。结论:环境暴露,尤其是早产儿对乙酰氨基酚的摄入可调节CYP2E1的代谢活性。
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