Placental microRNA methylome signatures may serve as biomarkers and therapeutic targets for prenatally opioid-exposed infants with neonatal opioid withdrawal syndrome

Frontiers in Genetics

Genetics

Swapan K. Nath¹  Lavanya V. Uppala²  Avinash Veerappa³  Raghu P. Metpally⁴  Ray O. Bahado-Singh⁵  Sangeetha Vishweswaraiah⁵  Uppala Radhakrishna⁵  Lori M. Mausi⁵  Richard C. Crist⁶  Wade H. Berrettini⁷  Srinivas B. Muvvala⁸  Ariadna Forray⁸ 

[1] Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, Oklahoma City, OK, United States;College of Information Science and Technology, Peter Kiewit Institute, Omaha, NE, United States;Department of Genetics, Cell Biology and Anatomy College of Medicine, University of Nebraska Medical Center, Omaha, NE, United States;Department of Molecular and Functional Genomics, Danville, PA, United States;Department of Obstetrics and Gynecology, Oakland University William Beaumont School of Medicine, Royal Oak, MI, United States;Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States;Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States;Geisinger Clinic, Danville, PA, United States;Department of Psychiatry, Yale School of Medicine, New Haven, CT, United States;

关键词: MicroRNAs;    opioid use disorder (OUD);    neonatal opioid withdrawal syndrome (NOWS);    methylation;    biomarkers;   

DOI  :  10.3389/fgene.2023.1215472

 received in 2023-05-02, accepted in 2023-06-01,  发布年份 2023

来源: Frontiers

【 摘 要 】

Introduction: The neonate exposed to opioids in utero faces a constellation of withdrawal symptoms postpartum commonly called neonatal opioid withdrawal syndrome (NOWS). The incidence of NOWS has increased in recent years due to the opioid epidemic. MicroRNAs (miRNAs) are small non-coding RNA molecules that play a crucial role in gene regulation. Epigenetic variations in microRNAs (miRNAs) and their impact on addiction-related processes is a rapidly evolving area of research.Methods: The Illumina Infinium Methylation EPIC BeadChip was used to analyze DNA methylation levels of miRNA-encoding genes in 96 human placental tissues to identify miRNA gene methylation profiles as-sociated with NOWS: 32 from mothers whose prenatally opioid-exposed infants required pharmacologic management for NOWS, 32 from mothers whose prenatally opioid-exposed infants did not require treat-ment for NOWS, and 32 unexposed controls.Results: The study identified 46 significantly differentially methylated (FDR p-value ≤ 0.05) CpGs associated with 47 unique miRNAs, with a receiver operating characteristic (ROC) area under the curve (AUC) ≥0.75 including 28 hypomethylated and 18 hypermethylated CpGs as potentially associated with NOWS. These dysregulated microRNA methylation patterns may be a contributing factor to NOWS pathogenesis.Conclusion: This is the first study to analyze miRNA methylation profiles in NOWS infants and illustrates the unique role miRNAs might have in diagnosing and treating the disease. Furthermore, these data may provide a step toward feasible precision medicine for NOWS babies as well.

【 授权许可】

Unknown   
Copyright © 2023 Radhakrishna, Nath, Uppala, Veerappa, Forray, Muvvala, Metpally, Crist, Berrettini, Mausi, Vishweswaraiah and Bahado-Singh.