Epigenetic variation in OPRM1 gene in opioid-exposed mother-infant dyads

Autor:	David A. Nielsen, F. N. U. Nikita, Angela Nolin, Hira Shrestha, Marie J. Hayes, K. Daigle, L. Hoyo, Elisha M. Wachman, H. E. Jones
Rok vydání:	2018
Předmět:	0301 basic medicine Adult Receptors Opioid mu Logistic regression Epigenesis Genetic Andrology Cohort Studies 03 medical and health sciences Behavioral Neuroscience 0302 clinical medicine Pregnancy Genetics Medicine Humans Epigenetics Promoter Regions Genetic business.industry Infant Newborn Infant Promoter Methylation DNA Methylation medicine.disease Opioid-Related Disorders 030104 developmental biology Neurology CpG site Prenatal Exposure Delayed Effects Cohort DNA methylation Female business Neonatal Abstinence Syndrome 030217 neurology & neurosurgery
Zdroj:	Genes, brain, and behavior. 17(7)
ISSN:	1601-183X
Popis:	Neonatal abstinence syndrome (NAS) due to in-utero opioid exposure has significant variability of severity. Preliminary studies have suggested that epigenetic variation within the μ-opioid receptor (OPRM1) gene impacts NAS. We aimed to determine if DNA methylation in OPRM1 within opioid-exposed mother-infant dyads is associated with differences in NAS severity in an independent cohort. Full-term opioid-exposed newborns and their mothers (N = 68 pairs) were studied. A DNA sample was obtained and then assessed for level of DNA methylation at 20 CpG sites within the OPRM1 promoter region by next-generation sequencing. Infants were monitored for NAS and treated with replacement opioids according to institutional protocol. The association between DNA methylation level at each CpG site with NAS outcome measures was evaluated using linear and logistic regression models. Higher methylation levels within the infants at the -18 (11.4% vs 4.4%, P = .0001), -14 (46.1% vs 24.0%, P = .002) and +23 (26.3% vs 12.9%, P = .008) CpG sites were associated with higher rates of infant pharmacologic treatment. Higher levels of methylation within the mothers at the -169 (R = 0.43, P = .008), -152 (R = 0.40, P = .002) and +84 (R = 0.44, P = .006) sites were associated point-wise with longer infant length of stay. Maternal associations remained significant point-wise for -169 (β = 0.07, P = .007) and on an experiment-wise level for +84 (β = -0.10, P = .003) using regression models. These results suggest an association of higher levels of OPRM1 methylation at specific CpG sites and increased NAS severity, replicating prior findings. These findings have important implications for personalized treatment regimens for infants at high risk for severe NAS.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::296c2a1c00fdbbf79e8d1076c28e5378 https://pubmed.ncbi.nlm.nih.gov/31273953 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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