Document Detail

Opioid receptor polymorphism A118G associated with clinical severity in a drug overdose population.
MedLine Citation:
PMID:  23318993     Owner:  NLM     Status:  MEDLINE    
Genetic variations in the human mu-opioid receptor gene (OPRM1) mediate individual differences in response to pain and opiate addiction. We studied whether the common A118G (rs1799971) mu-opioid receptor single nucleotide polymorphism (SNP) was associated with overdose severity in humans. In addition, we examined an SNP responsible for alternative splicing of OPRM1 (rs2075572). We assessed allele frequencies of the above SNPs and associations with clinical severity in patients presenting to the emergency department (ED) with acute drug overdose. This work was designed as an observational cohort study over a 12-month period at an urban teaching hospital. Participants consisted of consecutive adult ED patients with suspected acute drug overdose for whom discarded blood samples were available for analysis. Specimens were linked with clinical variables (demographics, urine toxicology screens, clinical outcomes) then deidentified prior to genetic SNP analysis. Blinded genotyping was performed after standard DNA purification and whole genome amplification. In-hospital severe outcomes were defined as either respiratory arrest (RA; defined by mechanical ventilation) or cardiac arrest (CA; defined by loss of pulse). We analyzed 179 patients (61% male, median age 32) who overall suffered 15 RAs and four CAs, of whom three died. The 118G allele conferred 5.3-fold increased odds of CA/RA (p<0.05), while the rs2075572 variant allele was not associated with CA/RA. The 118G variant allele in the OPRM1 gene is associated with worse clinical severity in patients with acute drug overdose. These findings mark the first time that the 118G variant allele is linked with clinical drug overdose vulnerability.
A F Manini; M M Jacobs; D Vlahov; Y L Hurd
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of medical toxicology : official journal of the American College of Medical Toxicology     Volume:  9     ISSN:  1937-6995     ISO Abbreviation:  J Med Toxicol     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-20     Completed Date:  2013-12-17     Revised Date:  2014-06-03    
Medline Journal Info:
Nlm Unique ID:  101284598     Medline TA:  J Med Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  148-54     Citation Subset:  IM    
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MeSH Terms
Alternative Splicing
Amino Acid Substitution
Benzodiazepines / toxicity*
Cohort Studies
Drug Overdose / blood,  genetics*,  metabolism,  physiopathology
Follow-Up Studies
Genetic Association Studies
Genetic Predisposition to Disease
Heart Arrest / etiology
Narcotics / toxicity*
Pilot Projects
Polymorphism, Single Nucleotide*
Prospective Studies
Receptors, Opioid, mu / genetics*,  metabolism
Respiratory Insufficiency / etiology
Severity of Illness Index
Sympathomimetics / toxicity*
United States
Grant Support
Reg. No./Substance:
0/Narcotics; 0/OPRM1 protein, human; 0/Receptors, Opioid, mu; 0/Sympathomimetics; 12794-10-4/Benzodiazepines
Comment In:
J Med Toxicol. 2013 Sep;9(3):292-3   [PMID:  23860727 ]

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