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Increased DNA Methylation of ABCB1, CYP2D6, and OPRM1 Genes in Newborn Infants of Methadone-Maintained Opioid-Dependent Mothers.
McLaughlin, Poppy; Mactier, Helen; Gillis, Cheryl; Hickish, Tamas; Parker, Anton; Liang, Wei-Jun; Osselton, M David.
Afiliação
  • McLaughlin P; Department of Archaeology, Anthropology, and Forensic Science, Bournemouth University, Poole, United Kingdom.
  • Mactier H; Neonatal Unit, Princess Royal Maternity, Glasgow, United Kingdom. Electronic address: helen.mactier@ggc.scot.nhs.uk.
  • Gillis C; Neonatal Unit, Princess Royal Maternity, Glasgow, United Kingdom.
  • Hickish T; Department of Molecular Pathology, Royal Bournemouth Hospital, Bournemouth, United Kingdom.
  • Parker A; Department of Molecular Pathology, Royal Bournemouth Hospital, Bournemouth, United Kingdom.
  • Liang WJ; Department of Archaeology, Anthropology, and Forensic Science, Bournemouth University, Poole, United Kingdom.
  • Osselton MD; Department of Archaeology, Anthropology, and Forensic Science, Bournemouth University, Poole, United Kingdom.
J Pediatr ; 190: 180-184.e1, 2017 11.
Article em En | MEDLINE | ID: mdl-28867064
OBJECTIVE: To investigate whether in utero opioid exposure, which has been linked to adverse neurodevelopmental and social outcomes, is associated with altered DNA methylation of opioid-related genes at birth. STUDY DESIGN: Observational cohort study of 21 healthy methadone-maintained opioid-dependent mother-infant dyads consecutively delivered at >36 weeks of gestation, and 2 comparator groups: smoking, "deprived" opioid-naïve mother-infant dyads (n = 17) and nonsmoking, "affluent" opioid-naïve mother-infant dyads (n = 15). DNA methylation of ABCB1, CYP2D6, and OPRM1 genes for mothers and babies was determined from buccal swabs. Plasma methadone concentrations were additionally measured for methadone-maintained opioid-dependent mothers. RESULTS: DNA methylation for ABCB1 and CYP2D6 was similar in opioid-naïve infants compared with their mothers, but was less for OPRM1 (3 ± 1.6% vs 8 ± 1%, P < .0005). Opioid-exposed newborns had similar DNA methylation to their mothers for all genes studied and greater methylation of ABCB1 (18 ± 4.8% vs 3 ± 0.5%), CYP2D6 (92 ± 1.2% vs 89 ± 2.4%), and OPRM1 (8 ± 0.3% vs 3 ± 1.6%) compared with opioid-naïve newborns (P < .0005 for all 3 genes). Infant DNA methylation was not related to birth weight, length of hospital stay, maternal smoking, dose or plasma concentration of methadone at delivery, or postcode of residence. CONCLUSIONS: In utero exposure to opioids is associated with increased methylation of opioid-related genes in the newborn infant. It is not clear whether these findings are due to opioid exposure per se or other associated lifestyle factors.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Efeitos Tardios da Exposição Pré-Natal / Receptores Opioides mu / Citocromo P-450 CYP2D6 / Metilação de DNA / Tratamento de Substituição de Opiáceos Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Adult / Female / Humans / Newborn / Pregnancy Idioma: En Revista: J Pediatr Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Reino Unido País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Efeitos Tardios da Exposição Pré-Natal / Receptores Opioides mu / Citocromo P-450 CYP2D6 / Metilação de DNA / Tratamento de Substituição de Opiáceos Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Risk_factors_studies Limite: Adult / Female / Humans / Newborn / Pregnancy Idioma: En Revista: J Pediatr Ano de publicação: 2017 Tipo de documento: Article País de afiliação: Reino Unido País de publicação: Estados Unidos