TY - JOUR
T1 - Opioid receptor gene (OPRM1, OPRK1, and OPRD1) variants and response to naltrexone treatment for alcohol dependence
T2 - Results from the VA Cooperative Study
AU - Gelernter, Joel
AU - Gueorguieva, Ralitza
AU - Kranzler, Henry R.
AU - Zhang, Huiping
AU - Cramer, Joyce
AU - Rosenheck, Robert
AU - Krystal, John H.
AU - Drexler, K.
AU - Hermos, J.
AU - Rugle, L.
AU - Kausch, O.
AU - Adinoff, B.
AU - Grabowski, J.
AU - Wancha, R.
AU - Madlock, L.
AU - FeBornstein, M.
AU - Pena, J.
AU - Casadonte, P.
AU - Nixon, S.
AU - Shaw, C.
AU - Haynes-Tucker, L.
AU - Moffet, L.
AU - Maany, I.
AU - Kaplan, G.
AU - Stock, C.
AU - Banys, P.
AU - Saxon, A.
AU - Krol, W.
AU - Miller, M.
PY - 2007/4
Y1 - 2007/4
N2 - 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 μ 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 μ, δ, and κ 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.
AB - 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 μ 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 μ, δ, and κ 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.
KW - Alcohol Dependence Treatment
KW - Naltrexone
KW - OPRD1
KW - OPRK1
KW - OPRM1
KW - Opioid Receptor Genes
KW - Pharmacogenetics
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UR - http://www.scopus.com/inward/citedby.url?scp=33947289675&partnerID=8YFLogxK
U2 - 10.1111/j.1530-0277.2007.00339.x
DO - 10.1111/j.1530-0277.2007.00339.x
M3 - Article
C2 - 17374034
AN - SCOPUS:33947289675
SN - 0145-6008
VL - 31
SP - 555
EP - 563
JO - Alcoholism: Clinical and Experimental Research
JF - Alcoholism: Clinical and Experimental Research
IS - 4
ER -