Placental cytochrome P450 methylomes in infants exposed to prenatal opioids: exploring the effects of neonatal opioid withdrawal syndrome on health horizons.
Placental cytochrome P450 methylomes in infants exposed to prenatal opioids: exploring the effects of neonatal opioid withdrawal syndrome on health horizons.
复制标题
DOI：
10.3389/fgene.2023.1292148
复制
发表时间：
2023
影响因子：
3.7
通讯作者：
Nath, Swapan K.
中科院分区：
文献类型：
--
作者：
Radhakrishna, Uppala;Sadhasivam, Senthilkumar;Radhakrishnan, Rupa;Forray, Ariadna;Muvvala, Srinivas B.;Metpally, Raghu P.;Patel, Saumya;Rawal, Rakesh M.;Vishweswaraiah, Sangeetha;Bahado-Singh, Ray O.;Nath, Swapan K.
背景：新生儿阿片类药物戒断综合征（NOWS）是由于妊娠期间阿片类药物使用增加而引起的。细胞色素P450（CYP 450）酶在人体内代谢多种物质，包括阿片类药物，其他药物，毒素和内源性化合物中起着关键作用。α-甲基化和阿片类药物作用之间的联系尚未研究，它可以提供有希望的见解。 目的：探讨产前阿片类药物暴露对婴儿CYP破坏的影响及其预期的长期临床意义。 研究设计：使用Illumina Infinium MethylationEPIC（850 k）BeadChips分析了96个胎盘组织的队列中的CD 45基因的DNA甲基化水平。这涉及三组胎盘组织：32例来自产前暴露于阿片类药物的婴儿需要NOWS药物治疗的母亲，32例来自产前暴露于阿片类药物的婴儿不需要NOWS治疗的母亲，32例来自未暴露的对照母亲。 结果如下：该研究确定了20个与17个不同的CpG基因相关的显著差异甲基化CpG位点，其中14个CpG在14个基因中显示甲基化降低（CYP 19 A1、CYP 1A 2、CYP 4V 2、CYP 1B 1、CYP 24 A1、CYP 26 B1、CYP 26 C1、CYP 2C 18、CYP 2C 9、CYP 2U 1、CYP 39 A1、CYP 2 R1、CYP 4 Z1、CYP 2D 7 P1和），而8个表现出高甲基化（CYP 51 A1、CYP 26 B1、CYP 2 R1、CYP 2U 1、CYP 4X 1、CYP 1A 2、CYP 2 W1和CYP 4V 2）。CYP 1A 2、CYP 26 B1、CYP 2 R1、CYP 2U 1和CYP 4V 2等基因均表现出甲基化增加和减少。这些基因对于代谢类花生酸、脂肪酸、药物和各种物质至关重要。 结论：该研究确定了与NOWS相关的胎盘组织中多个mRNA基因的深刻甲基化变化。这表明，DNA甲基化模式的破坏可能在NOWS中发挥作用，并可能作为有价值的生物标志物，提示个性化治疗的未来途径。需要进一步的研究来证实这些发现，并探索其诊断和治疗的潜力。
Background: Neonatal opioid withdrawal syndrome (NOWS), arises due to increased opioid use during pregnancy. Cytochrome P450 (CYP) enzymes play a pivotal role in metabolizing a wide range of substances in the human body, including opioids, other drugs, toxins, and endogenous compounds. The association between CYP gene methylation and opioid effects is unexplored and it could offer promising insights. Objective: To investigate the impact of prenatal opioid exposure on disrupted CYPs in infants and their anticipated long-term clinical implications. Study Design: DNA methylation levels of CYP genes were analyzed in a cohort of 96 placental tissues using Illumina Infinium MethylationEPIC (850 k) BeadChips. This involved three groups of placental tissues: 32 from mothers with infants exposed to opioids prenatally requiring pharmacologic treatment for NOWS, 32 from mothers with prenatally opioid-exposed infants not needing NOWS treatment, and 32 from unexposed control mothers. Results: The study identified 20 significantly differentially methylated CpG sites associated with 17 distinct CYP genes, with 14 CpGs showing reduced methylation across 14 genes (CYP19A1, CYP1A2, CYP4V2, CYP1B1, CYP24A1, CYP26B1, CYP26C1, CYP2C18, CYP2C9, CYP2U1, CYP39A1, CYP2R1, CYP4Z1, CYP2D7P1 and), while 8 exhibited hypermethylation (CYP51A1, CYP26B1, CYP2R1, CYP2U1, CYP4X1, CYP1A2, CYP2W1, and CYP4V2). Genes such as CYP1A2, CYP26B1, CYP2R1, CYP2U1, and CYP4V2 exhibited both increased and decreased methylation. These genes are crucial for metabolizing eicosanoids, fatty acids, drugs, and diverse substances. Conclusion: The study identified profound methylation changes in multiple CYP genes in the placental tissues relevant to NOWS. This suggests that disruption of DNA methylation patterns in CYP transcripts might play a role in NOWS and may serve as valuable biomarkers, suggesting a future pathway for personalized treatment. Further research is needed to confirm these findings and explore their potential for diagnosis and treatment.
登录
查看更多内容
影响因子：
8
作者：
Fill MA;Miller AM;Wilkinson RH;Warren MD;Dunn JR;Schaffner W;Jones TF
通讯作者：
Jones TF
DOI：
10.1016/j.jmhi.2013.02.001
发表时间：
2013-07-01
期刊：
JOURNAL OF MEDICAL HYPOTHESES AND IDEAS
影响因子：
--
作者：
Eserian, Jaqueline Kalleian
通讯作者：
Eserian, Jaqueline Kalleian
影响因子：
2.5
作者：
Brady KT;Haynes LF;Hartwell KJ;Killeen TK
通讯作者：
Killeen TK
DOI：
10.3390/ijerph18052225
发表时间：
2021-02-24
影响因子：
--
作者：
Garduno A;Wu T
通讯作者：
Wu T
影响因子：
3.4
作者：
Colebatch, Andrew J.;Dobrovic, Alexander;Cooper, Wendy A.
通讯作者：
Cooper, Wendy A.