A mu opioid receptor gene polymorphism (A118G) and naltrexone treatment response in adherent Korean alcohol-dependent patients

Kim, Sung‐Gon; Kim, Cheol-Min; Choi, Sam‐Wook; Jae, Young Myo; Lee, Hae-Gook; Son, Bongki; Kim, Jeong-Gee; Choi, Young Bong; Kim, Han-Oh; Kim, Seong-Yeon; Oslin, David W.

doi:10.1007/s00213-008-1330-5

Cited by 80 publications

(66 citation statements)

References 47 publications

(54 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This is an important empirical and clinical question for two reasons. First, the minor Asp40 allele of the OPRM1 gene found to predict a more positive response to naltrexone in the human laboratory (Ray and Hutchison, 2007a) and in clinical trials (Anton et al, 2008;Kim et al, 2009;Oslin et al, 2003) is markedly more prevalent among individuals of Asian descent (Arias et al, 2006). Second, the vast majority of the pharmacogenetic studies completed to date have been in Caucasian samples.…”

Section: Discussionmentioning

confidence: 99%

“…Only two studies have examined the moderating role of the OPRM1 Asn40Asp SNP in response to opioid blockade in individuals of Asian descent. One was a clinical trial of naltrexone in Korean alcohol-dependent patients who found a positive pharmacogenetic effect when restricting the analyses to individuals who were medication compliant (Kim et al, 2009). The other study compared HPA-axis activation in response to a naloxone challenge among Caucasians and individuals of Asian descent and found that the pharmacogenetic effect was populationspecific and was only observed in Caucasians (HernandezAvila et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Consistent with this hypothesis, individuals with the Asp40 allele demonstrate enhanced hypothalamic-pituitary-axis (HPA) dynamics in response to an opiate blockade (Wand et al, 2002), enhanced cortisol response, and reduced agonist effect of morphine-6-glucuronide after treatment with naloxone (Hernandez-Avila et al, 2003), greater naltrexone-induced blunting of alcohol high (Ray and Hutchison, 2007a), and lower relapse rates in clinical trials of naltrexone for alcoholism (Anton et al, 2008;Oslin et al, 2003). A study of Korean alcohol-dependent patients found that carriers of the Asp40 allele took longer to relapse, but these effects were only observed among treatment adherent patients (Kim et al, 2009). Some studies, however, have failed to support this pharmacogenetic effect Tidey et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacogenetics of Naltrexone in Asian Americans: A Randomized Placebo-Controlled Laboratory Study

Ray

Bujarski

Chin

et al. 2011

Neuropsychopharmacol

View full text Add to dashboard Cite

Recent clinical and laboratory studies have shown that the effects of naltrexone for alcoholism may be moderated by the Asn40Asp single-nucleotide polymorphism (SNP) of the m-opioid receptor gene (OPRM1). Allele frequencies for this polymorphism, however, have been shown to vary substantially as a function of ethnic background, such that individuals of Asian descent are more likely to carry the minor (Asp40) allele. The objective of this study is to test the naltrexone pharmacogenetic effects of the Asn40Asp SNP in a sample of Asian Americans. This study consists of a double-blinded, randomized, placebo-controlled laboratory trial of naltrexone. Participants (n ¼ 35, 10 females; 13 Asn40Asn and 22 Asp40 carriers) were non-treatment-seeking heavy drinkers recruited from the community. After taking naltrexone or placebo, participants completed an intravenous alcohol administration session. The primary outcome measures were subjective intoxication and alcohol craving. Results suggested that Asp40 carriers experienced greater alcohol-induced sedation, subjective intoxication, and lower alcohol craving on naltrexone, as compared to placebo, and to Asn40 homozygotes. There results were maintained when controlling for ALDH2 (rs671) and ADH1B (rs1229984) markers and when examining the three levels of OPRM1 genotype, thereby supporting an OPRM1 gene dose response. These findings provide a much-needed extension of previous studies of naltrexone pharmacogenetics to individuals of Asian descent, an ethnic group more likely to express the minor allele putatively associated with improved biobehavioral and clinical response to this medication. These findings help further delineate the biobehavioral mechanisms of naltrexone and its pharmacogenetics.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Pharmacogenetics of Naltrexone in Asian Americans: A Randomized Placebo-Controlled Laboratory Study

Ray

Bujarski

Chin

et al. 2011

Neuropsychopharmacol

View full text Add to dashboard Cite

show abstract

“…It should be noted that the sole haplotype that was associated with naltrexone response was the one carrying the 118G allele. In a diff erent prospective study in 63 alcohol-dependent Korean patients treated with naltrexone 25mg/day for fi rst 3 days and 50mg/day for the remaining days ofa 12-week treatment, Kim and colleagues have found that patients with at least one 118G allele took signifi cantly longer time to relapse than 118AA homozygotes [39]. Th ese results highlight that the association of OPRM1 A118G polymorphism with naltrexone responseoutscales potential ethnic diff erences.…”

Section: Introductionmentioning

confidence: 99%

Pharmacogenomics of alcohol addiction: Personalizing pharmacologic treatment of alcohol dependence

Ragia¹,

Manolopoulos²

2014

Hosp Pharm Int Multi J

View full text Add to dashboard Cite

SUMMARYAlcohol dependence is a serious psychiatric disorder with harmful physical, mental and social consequences, and a high probability of a chronic relapsing course. The fi eld of pharmacologic treatment of alcohol dependence and craving is expanding rapidly; the drugs that have been found to reduce relapse rates or drinking in alcohol-dependent patients and are approved for treatment of alcohol dependence are naltrexone, acamprosate and disulfi ram, whereas also topiramate appears as a promising therapy. For many patients, however, these treatments are not eff ective. Evidence from a number of diff erent studies suggests that genetic variation is a signifi cant contributor to interindividual variation of clinical presentation of alcohol problems and response to a given treatment. The aim of the present review is to summarize and discuss the fi ndings on the association between gene polymorphisms and the response to alcohol dependence treatment medications. It is anticipated that future implementation of pharmacogenomics in clinical practice will help personalize alcohol dependence drug treatment, and development personalized hospital pharmacology.

show abstract

“…An association of variations in the kappa-opioid system with alcohol dependence has also been described (Xuei et al, 2006). The OPRM1 118G genotype may moderate the subjective and neuronal response of opioid antagonists on alcohol and alcohol cue reactivity (Ashenhurst et al, 2012;Setiawan et al, 2012;Schacht et al, 2013) and modify response to treatment with opioid antagonists such as naltrexone, although there are conflicting results (Oslin et al, 2003;McGeary et al, 2006;Gelernter et al, 2007;Anton et al, 2008Anton et al, , 2012Kim et al, 2009;Koller et al, 2012;Oroszi et al, 2009;Kranzler et al, 2013). A recent metaanalysis supported the role of the A118G polymorphism of the OPRM1 gene in moderating the effect of naltrexone in patients with alcohol dependence and treatment response (Chamorro et al, 2012).…”

Section: Nalmefene For Alcohol Dependence 679mentioning

confidence: 99%

Nalmefene for the treatment of alcohol dependence: a current update

Soyka

2013

Int. J. Neuropsychopharm.

View full text Add to dashboard Cite

To date, few pharmacotherapies have been established for the treatment of alcoholism. There is a plethora of research concerning the involvement of the opioid-endorphin system in mediating the reinforcing effects of alcohol. The opioid antagonist naltrexone has been found to be effective in alcohol treatment. In addition, the mu-opioid antagonist and partial kappa agonist nalmefene was recently approved by the European Medicines Agency for the treatment of alcoholism. The relevant studies followed a harm-reduction, 'as needed' approach and showed a reduction in alcohol consumption with nalmefene 20 mg rather than increased abstinence rates, (which was not the primary goal of the relevant studies). The available literature is reviewed and discussed. Nalmefene appears to be a safe and effective treatment for alcohol dependence.

show abstract

A mu opioid receptor gene polymorphism (A118G) and naltrexone treatment response in adherent Korean alcohol-dependent patients

Cited by 80 publications

References 47 publications

Pharmacogenetics of Naltrexone in Asian Americans: A Randomized Placebo-Controlled Laboratory Study

Pharmacogenetics of Naltrexone in Asian Americans: A Randomized Placebo-Controlled Laboratory Study

Pharmacogenomics of alcohol addiction: Personalizing pharmacologic treatment of alcohol dependence

Nalmefene for the treatment of alcohol dependence: a current update

Contact Info

Product

Resources

About