Human mu opioid receptor gene polymorphisms and vulnerability to substance abuse

Berrettini, Wade H.; Hoehe, Margret R.; Ferraro, Thomas N.; DeMaria, Peter A.; Gottheil, Edward

doi:10.1080/13556219772598

Cited by 78 publications

(71 citation statements)

References 21 publications

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“…For example, we didn't find the c.17C→T SNP in our tested population, although the frequency of the SNP was once reported 10% in healthy Caucasian and African-American volunteers and 22% in cocaine/opioid addicts (Berrettini et al, 1997). Consistent with this observation, the frequency of the c.17C→T SNP varied significantly in other case reports of different populations (Bond et al, 1998;Bergen et al, 1997).…”

Section: Discussionsupporting

confidence: 80%

Sequence variations in the mu-opioid receptor gene (OPRM1) associated with human addiction to heroin

Shi¹,

Hui²,

Xu³

et al. 2002

Hum. Mutat.

122

100

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Human mu-opioid receptor (OPRM1) is the major site for the analgesic action of most opioid drugs such as morphine, methadone and heroin. It was previously reported that a single nucleotide polymorphism (SNP) in exon1 (c.118A→G) of OPRM1 might modestly alter the affinity in beta-endorphin-Mu interaction. Using denaturing high performance liquid chromatography (DHPLC) the complete coding region of the OPRM1 gene was screened for SNPs in Han-Chinese heroin addicts and normal control. Three novel SNPs were detected, one in exon3, one in intron3 and one in the 3' untranslated region. The SNP c.118A→G reportedly altered the interaction of Mu receptor with opioid had no statistically significant correlation with heroin addition in Han Chinese. However, addicted subjects with the SNP in intron2 (IVS2 +31G→A) tended to show much higher heroin intake dosages than those without this SNP. We also observed that individuals carrying both SNP c.118A→G and IVS2 +31G→A consumed relatively more drugs compared to other addicts. Thus our study further highlights the importance of studing the various regions of the mu opioid receptor gene, coding as well as non-coding, for genetic markers that may be linked to, or directly contribute to opioid drug-seeking behavior.

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Section: Discussionsupporting

confidence: 80%

Sequence variations in the mu-opioid receptor gene (OPRM1) associated with human addiction to heroin

Shi¹,

Hui²,

Xu³

et al. 2002

Hum. Mutat.

122

100

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“…The allelic frequency of 17T has ranged from 0.8 to 21% across ethnic groups (Berrettini et al, 1997;Bond et al, 1998;Gelernter et al, 1999). A trend (p ¼ 0.054 or p ¼ 0.05 Bond et al and Berrettini et al, respectively) towards a higher frequency of this variant and substance dependence has also been reported (Berrettini et al, 1997;Bond et al, 1998). As this variant, the second most frequently occurring SNP within exon 1 of OPRM1, was not identified, haplotype analysis incorporating this SNP could not be performed.…”

Section: A118g Snp and Alcohol Dependence In Central Sweden G Bart Et Almentioning

confidence: 99%

Increased Attributable Risk Related to a Functional μ-Opioid Receptor Gene Polymorphism in Association with Alcohol Dependence in Central Sweden

Bart

Kreek

Ott

et al. 2004

Neuropsychopharmacol

197

130

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The m-opioid receptor (MOR), through its effects on reward and stress-responsivity, modulates alcohol intake in both animal and human laboratory studies. We have previously demonstrated that the frequently occurring A118G single-nucleotide polymorphism (SNP) in exon 1 of the MORgene (OPRM1), which encodes an amino-acid substitution, is functional and receptors encoded by the variant 118G allele bind the endogenous opioid peptide b-endorphin with three-fold greater affinity than prototype receptors. Other groups subsequently reported that this variant alters stress-responsivity in normal volunteers and also increases the therapeutic response to naltrexone (a m-preferring opioid antagonist) in the treatment of alcohol dependence. We compared frequencies of genotypes containing an 118G allele in 389 alcohol-dependent individuals and 170 population-based controls without drug or alcohol abuse or dependence. The A118G SNP was present in the Hardy-Weinberg equilibrium with an overall frequency of the 118G allele of 10.9%. There was a significant overall association between genotypes with an 118G allele and alcohol dependence (p ¼ 0.0074). The attributable risk for alcohol dependence in subjects with an 118G allele was 11.1%. There was no difference in A118G genotype between type 1 and type 2 alcoholics. In central Sweden, the functional variant 118G allele in exon 1 of OPRM1 is associated with an increased attributable risk for alcohol dependence.

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“…In particular, two polymorphisms in exon 1 of the gene alter amino acid sequence, A +118 G (Asn40Asp) and C +17 T (Ala6Val), and these have received the most research attention. However, case-control studies have failed to demonstrate a consistent association between OPRM1 sequence variation and the presence of alcohol and/or drug dependence (Bergen et al, 1997;Berrettini et al, 1997;Bond et al, 1998;Kranzler et al, 1998;Sander et al, 1998;Gelernter et al, 1999;Town et al, 1999;Hoehe et al, 2000;Franke et al, 2001;Rommelspacher et al, 2001;Szeto et al, 2001;Schinka et al, 2002;Crowley et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

A Functional Polymorphism of the μ-Opioid Receptor Gene is Associated with Naltrexone Response in Alcohol-Dependent Patients

Oslin

Berrettini

Kranzler

et al. 2003

Neuropsychopharmacol

546

399

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This study examined the association between two specific polymorphisms of the gene encoding the m-opioid receptor and treatment outcomes in alcohol-dependent patients who were prescribed naltrexone or placebo. A total of 82 patients (71 of European descent) who were randomized to naltrexone and 59 who were randomized to placebo (all of European descent) in one of three randomized, placebo-controlled clinical trials of naltrexone were genotyped at the A +118 G (Asn40Asp) and C +17 T (Ala6Val) SNPs in the gene encoding the m-opioid receptor (OPRM1). The association between genotype and drinking outcomes was measured over 12 weeks of treatment. In subjects of European descent, individuals with one or two copies of the Asp40 allele treated with naltrexone had significantly lower rates of relapse (p ¼ 0.044) and a longer time to return to heavy drinking (p ¼ 0.040) than those homozygous for the Asn40 allele. There were no differences in overall abstinence rates (p ¼ 0.611), nor were there differences in relapse rates or abstinence rates between the two genotype groups among those assigned to placebo. These preliminary results are consistent with prior literature demonstrating that the opioid system is involved in the reinforcing properties of alcohol and that allelic variation at OPRM1 is associated with differential response to a m-receptor antagonist. If replicated, these results would help to identify alcohol-dependent individuals who may be most likely to respond to treatment with naltrexone.

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Human mu opioid receptor gene polymorphisms and vulnerability to substance abuse

Cited by 78 publications

References 21 publications

Sequence variations in the mu-opioid receptor gene (OPRM1) associated with human addiction to heroin

Sequence variations in the mu-opioid receptor gene (OPRM1) associated with human addiction to heroin

Increased Attributable Risk Related to a Functional μ-Opioid Receptor Gene Polymorphism in Association with Alcohol Dependence in Central Sweden

A Functional Polymorphism of the μ-Opioid Receptor Gene is Associated with Naltrexone Response in Alcohol-Dependent Patients

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