Elisha M Wachman1, Marie J Hayes2, Richard Sherva3, Mark S Brown4, Jonathan M Davis5, Lindsay A Farrer6, David A Nielsen7. 1. Pediatrics, Boston Medical Center, 771 Albany Street, Dowling 4N 4109, Boston, MA 02118, United States. Electronic address: Elisha.Wachman@bmc.org. 2. Graduate School of Biomedical Science & Engineering, University of Maine, Orono, ME 04469, United States. Electronic address: mhayes@maine.edu. 3. Biomedical Genetics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, United States. Electronic address: sherva@bu.edu. 4. Pediatrics, Eastern Maine Medical Center, 489 State St, Bangor, ME 04401, United States. Electronic address: mbrown@emhs.org. 5. Pediatrics, The Floating Hospital for Children at Tufts Medical Center, 755 Washington Street, Boston, MA 02116, United States. Electronic address: jdavis@tuftsmedicalcenter.org. 6. Biomedical Genetics, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118, United States. Electronic address: farrer@bu.edu. 7. Psychology, Baylor College of Medicine, 1 Baylor Plaza, Houston, TX 77030, United States. Electronic address: nielsen@bcm.edu.
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.
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 PNOCrs732636 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 OPRK1rs702764 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 COMTrs740603 A allele (β=-5.3 days, p=0.01) were associated with shorter LOS. The OPRD1rs204076 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: Elisha M Wachman; P K Newby; Joy Vreeland; John Byun; Anthony Bonzagni; Howard Bauchner; Barbara L Philipp Journal: J Addict Med Date: 2011-12 Impact factor: 3.702
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