title: Variations in opioid receptor genes in neonatal abstinence syndrome.
abstract: BACKGROUND
  There is significant variability in the severity of neonatal abstinence syndrome (NAS) due to in-utero opioid exposure. We wanted to determine if single nucleotide polymorphisms (SNPs) in key candidate genes contribute to this variability.
  
  
  METHODS
  Full-term opioid-exposed newborns and their mothers (n=86 pairs) were studied. DNA was genotyped for 80 SNPs from 14 genes utilizing a custom designed microarray. The association of each SNP with NAS outcomes was evaluated.
  
  
  RESULTS
  SNPs in two opioid receptor genes in the infants were associated with worse NAS severity: (1) The PNOC rs732636 A allele (OR=3.8, p=0.004) for treatment with 2 medications and a longer hospital stay (LOS) of 5.8 days (p=0.01), and (2) The OPRK1 rs702764 C allele (OR=4.1, p=0.003) for treatment with 2 medications. The OPRM1 rs1799971 G allele (β=-6.9 days, p=0.02) and COMT rs740603 A allele (β=-5.3 days, p=0.01) were associated with shorter LOS. The OPRD1 rs204076 A allele in the mothers was associated with a longer LOS by 6.6 days (p=0.008). Results were significant point-wise but did not meet the experiment-wide significance level.
  
  
  CONCLUSIONS
  These findings suggest that SNPs in opioid receptor and the PNOC genes are associated with NAS severity. However, further testing in a large sample is warranted. This has important implications for prenatal prediction and personalized treatment regimens for infants at highest risk for severe NAS.
authors.affiliation: Pediatrics, Boston Medical Center, 771 Albany Street, Dowling 4N 4109, Boston, MA 02118, United States. Electronic address: Elisha.Wachman@bmc.org.
authors.forename: Elisha M
authors.initials: EM
authors.lastname: Wachman
authors.affiliation: Graduate School of Biomedical Science & Engineering, University of Maine, Orono, ME 04469, United States. Electronic address: mhayes@maine.edu.
authors.forename: Marie J
authors.initials: MJ
authors.lastname: Hayes
authors.affiliation: Biomedical Genetics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, United States. Electronic address: sherva@bu.edu.
authors.forename: Richard
authors.initials: R
authors.lastname: Sherva
authors.affiliation: Pediatrics, Eastern Maine Medical Center, 489 State St, Bangor, ME 04401, United States. Electronic address: mbrown@emhs.org.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Brown
authors.affiliation: Pediatrics, The Floating Hospital for Children at Tufts Medical Center, 755 Washington Street, Boston, MA 02116, United States. Electronic address: jdavis@tuftsmedicalcenter.org.
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Davis
authors.affiliation: Biomedical Genetics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, United States. Electronic address: farrer@bu.edu.
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
authors.affiliation: Psychology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, United States. Electronic address: nielsen@bcm.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Nielsen
mesh_terms: D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007902:Length of Stay; D046228:Microarray Analysis; D009357:Neonatal Abstinence Syndrome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics*; D011957:Receptors, Opioid / Q000235:genetics*; D017465:Receptors, Opioid, delta / Q000235:genetics*; D017473:Receptors, Opioid, kappa / Q000235:genetics*; D017450:Receptors, Opioid, mu / Q000235:genetics*
chemical_list: C529706:OPRD1 protein, human; C515653:OPRK1 protein, human; C485764:OPRM1 protein, human; D011498:Protein Precursors; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C121527:prepronociceptin; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: Genetics; Neonatal abstinence syndrome (NAS); Opioids; Single nucleotide polymorphisms (SNPs)