Placental OPRM1 DNA methylation and associations with neonatal opioid withdrawal syndrome, a pilot study

Epigenetic variation of DNA methylation of the mu-opioid receptor gene ( ) has been identified in the blood and saliva of individuals with opioid use disorder (OUD) and infants with neonatal opioid withdrawal syndrome (NOWS). It is unknown whether epigenetic variation in exists within placental tiss...

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Bibliographic Details
Published in:	Exploration of medicine Vol. 1; no. 3; pp. 124 - 135
Main Authors:	Wachman, Elisha M, Wang, Alice, Isley, Breanna C, Boateng, Jeffery, Beierle, Jacob A, Hansbury, Aaron, Shrestha, Hira, Bryant, Camron, Zhang, Huiping
Format:	Journal Article
Language:	English
Published:	United States Open Exploration Publishing Inc 01-06-2020
Subjects:	dna methylation epigenetics neonatal abstinence syndrome neonatal opioid withdrawal syndrome opioids oprm1 placenta neonatal opioid withdrawal syndrome neonatal abstinence syndrome DNA methylation placenta OPRM1 epigenetics opioids
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Summary:	Epigenetic variation of DNA methylation of the mu-opioid receptor gene ( ) has been identified in the blood and saliva of individuals with opioid use disorder (OUD) and infants with neonatal opioid withdrawal syndrome (NOWS). It is unknown whether epigenetic variation in exists within placental tissue in women with OUD and whether it is associated with NOWS outcomes. In this pilot study, the authors aimed to 1) examine the association between placental DNA methylation levels and NOWS outcomes, and 2) compare methylation levels in opioid-exposed non-exposed control placentas. Placental tissue was collected from eligible opioid ( = 64) and control ( = 29) women after delivery. Placental DNA was isolated and methylation levels at six cytosine-phosphate-guanine (CpG) sites within the promoter were quantified. Methylation levels were evaluated for associations with infant NOWS outcome measures: need for pharmacologic treatment, length of hospital stay (LOS), morphine treatment days, and treatment with two medications. Regression models were created and adjusted for clinical co-variates. Methylation levels between opioid and controls placentas were also compared. The primary opioid exposures were methadone and buprenorphine. Forty-nine (76.6%) of the opioid-exposed infants required pharmacologic treatment, 10 (15.6%) two medications, and average LOS for all opioid-exposed infants was 16.5 (standard deviation 9.7) days. There were no significant associations between DNA methylation levels in the six CpG sites and any NOWS outcome measures. No significant differences were found in methylation levels between the opioid and control samples. No significant associations were found between placental DNA methylation levels and NOWS severity in this pilot cohort. In addition, no significant differences were seen in methylation in opioid control placentas. Future association studies examining methylation levels on a genome-wide level are warranted.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 EMW and AW contributed to the conception and design of the study; HS and JAB organized the database; EMW wrote the first draft of the manuscript; BCI wrote sections of the manuscript; JAB and AH performed the data analysis; HS and BCI performed the subject enrollment, sample and data collection; AW performed the DNA isolation; JAB, CB, and HZ contributed to the analysis and interpretation of the data. All authors contributed to the manuscript revision, read and approved the submitted version. Author contributions
ISSN:	2692-3106
DOI:	10.37349/emed.2020.00009