title: Association of maternal and infant variants in PNOC and COMT genes with neonatal abstinence syndrome severity.
abstract: OBJECTIVE
  There is significant variability in severity of neonatal abstinence syndrome (NAS) due to in utero opioid exposure. Our previous study identified single nucleotide polymorphisms (SNPs) in the prepronociceptin (PNOC) and catechol-O-methyltransferase (COMT) genes that were associated with differences in NAS outcomes. This study looks at the same SNPs in PNOC and COMT in an independent cohort in an attempt to replicate previous findings.
  
  
  METHODS
  For the replication cohort, full-term opioid-exposed newborns and their mothers (n = 113 pairs) were studied. A DNA sample was obtained and genotyped for five SNPs in the PNOC and COMT genes. The association of each SNP with NAS outcomes (length of hospitalization, need for pharmacologic treatment, and total opioid days) was evaluated, with an experiment-wise significance level set at α < .003 and point-wise level of α < .05. SNP associations in a combined cohort of n = 199 pairs (replication cohort plus 86 pairs previously reported), were also examined.
  
  
  RESULTS
  In the replication cohort, mothers with the COMT rs4680 G allele had infants with a reduced risk for treatment with two medications for NAS (adjusted OR = .5, p = .04), meeting point-wise significance. In the combined cohort, infants with the PNOC rs4732636 A allele had a reduced need for medication treatment (adjusted OR 2.0, p = .04); mothers with the PNOC rs351776 A allele had infants who were treated more often with two medications (adjusted OR 2.3, p = .004) with longer hospitalization by 3.3 days (p = .01). Mothers with the COMT rs740603 A allele had infants who were less often treated with any medication (adjusted OR .5, p = .02). Though all SNP associations all met point wise and clinical significance, they did not meet the experiment-wise significance threshold.
  
  
  CONCLUSIONS
  We found differences in NAS outcomes depending on PNOC and COMT SNP genotype. This has important implications for identifying infants at risk for severe NAS who could benefit from tailored treatment regimens. Further testing in a larger sample is warranted. This has important implications for prenatal prediction and personalized treatment regimens for infants with NAS. (Am J Addict 2017;26:42-49).
authors.affiliation: Department of Pediatrics, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Elisha M
authors.initials: EM
authors.lastname: Wachman
authors.affiliation: Graduate School of Biomedical Science and Engineering, University of Maine, Orono, Maine.
authors.forename: Marie J
authors.initials: MJ
authors.lastname: Hayes
authors.affiliation: Department of Biomedical Genetics, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Richard
authors.initials: R
authors.lastname: Sherva
authors.affiliation: Department of Pediatrics, Eastern Maine Medical Center, Bangor, Maine.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Brown
authors.affiliation: Department of Pediatrics, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Hira
authors.initials: H
authors.lastname: Shrestha
authors.affiliation: Department of Transplant Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Logan
authors.affiliation: Department of Psychology, Siena College, Loudonville, New York.
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Heller
authors.affiliation: Department of Psychiatry, Baylor College of Medicine, Houston, Texas.
authors.forename: David A
authors.initials: DA
authors.lastname: Nielsen
authors.affiliation: Department of Biomedical Genetics, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
mesh_terms: D000483:Alleles; D000701:Analgesics, Opioid / Q000009:adverse effects*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D009035:Mothers; D009357:Neonatal Abstinence Syndrome / Q000175:diagnosis / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics*; D011957:Receptors, Opioid / Q000235:genetics*
chemical_list: D000701:Analgesics, Opioid; D011498:Protein Precursors; D011957:Receptors, Opioid; C121527:prepronociceptin; D002394:Catechol O-Methyltransferase