RGD Reference Report - Opioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence: results from the VA Cooperative Study. - Rat Genome Database

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Opioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence: results from the VA Cooperative Study.

Authors: Gelernter, Joel  Gueorguieva, Ralitza  Kranzler, Henry R  Zhang, Huiping  Cramer, Joyce  Rosenheck, Robert  Krystal, John H  VA Cooperative Study #425 Study Group,  
Citation: Gelernter J, etal., Alcohol Clin Exp Res. 2007 Apr;31(4):555-63. doi: 10.1111/j.1530-0277.2007.00339.x.
RGD ID: 401827944
Pubmed: PMID:17374034   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1530-0277.2007.00339.x   (Journal Full-text)


BACKGROUND: Pharmacotherapy of alcohol dependence (AD) is at an early stage of development; currently available medications have limited efficacy. It would be clinically valuable to identify, before initiation of a course of treatment, those patients who, based on genetic markers, are most likely to respond to a specific pharmacotherapy. A previous report suggested that a functional variant at the genetic locus encoding the mu opioid receptor (Asn40Asp) is such a marker, in short-term (3-month) treatment with the opioid-blocking drug naltrexone (NTX).
METHODS: We studied polymorphic variants at each of the 3 opioid receptor genes--OPRM1, OPRD1, and OPRK1, which encode the mu, delta, and kappa opioid receptors, respectively--including the OPRM1 Asn40Asp variant--as predictors of response to NTX or placebo in 215 alcohol-dependent male subjects who participated in Veterans Affairs Cooperative Study 425, "Naltrexone in the Treatment of Alcohol Dependence."
RESULTS: At the 3-month time point, treatment condition, age, and the pretreatment number of drinks per drinking day were all significant (p<0.05) predictors of the rate of relapse and time to relapse. Although NTX had no significant effect on relapse to heavy drinking in the overall sample in CSP 425, it significantly reduced relapse in the subgroup that provided DNA for analysis (i.e., the present study sample). There were no significant interactions between any individual single nucleotide polymorphisms studied and NTX treatment response.
CONCLUSIONS: These results do not support association of the OPRM1 Asn40Asp polymorphism with NTX treatment response for AD.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
OPRM1Humanalcohol dependence no_associationIAGP DNA:missense mutation:exon:p.N40D (118A>G) (rs 1799971) (human)RGD 
Oprm1Ratalcohol dependence no_associationISOOPRM1 (Homo sapiens)DNA:missense mutation:exon:p.N40D (118A>G) (rs 1799971) (human)RGD 
Oprm1Mousealcohol dependence no_associationISOOPRM1 (Homo sapiens)DNA:missense mutation:exon:p.N40D (118A>G) (rs 1799971) (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Oprm1  (opioid receptor, mu 1)

Genes (Mus musculus)
Oprm1  (opioid receptor, mu 1)

Genes (Homo sapiens)
OPRM1  (opioid receptor mu 1)


Additional Information