Association of a functional ?-opioid receptor allele (+118A) with alcohol dependency

Town, Terrence; Abdullah, Laila; Crawford, Fiona; Schinka, John A.; Ordorica, Patricia Isbell; Francis, Elie; Hughes, Patrick H.; Duara, Ranjan; Mullan, Michael

doi:10.1002/(sici)1096-8628(19991015)88:5<458::aid-ajmg3>3.0.co;2-s

Cited by 90 publications

(58 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A number of studies have reported positive association between OPRM1 functional variant A118G and OD, [27][28][29][30] cocaine dependence (CD) 31 or AD. [31][32][33][34] Moreover, three studies adopting haplotype-based approaches also demonstrated the association between OPRM1 variants and DD or AD. [35][36][37] However, a meta-analysis showed no consistent evidence of an association of the A118G polymorphism with SD.…”

Section: Introductionmentioning

confidence: 93%

The OPRD1 and OPRK1 loci in alcohol or drug dependence: OPRD1 variation modulates substance dependence risk

et al. 2007

View full text Add to dashboard Cite

Eleven single-nucleotide polymorphisms (SNPs) spanning OPRD1 were examined in 1063 European Americans (EAs) (620 cases with substance dependence (SD), including 557 with alcohol dependence (AD), 225 with cocaine dependence (CD) and 111 with opioid dependence (OD), and 443 controls). Nominally significant associations (P < 0.05) of five SNPs with SD were observed; only the association of the non-synonymous variant G80T with OD remained significant after correction for multiple testing using SNPSpD. Haplotype analyses with six tag SNPs indicated that a specific haplotype GCAACT, which harbors G80T G-allele and C921T C-allele, was significantly associated with AD (v 2 = 14.82, degrees of freedom (d.f.) = 1, P < 0.001), CD (v 2 = 9.19, d.f. = 1, P = 0.002) and OD (v 2 = 20.68, d.f. = 1, P < 0.001). Logistic regression analyses, with sex and age being considered, demonstrated that this haplotype had a risk effect on AD (P = 0.03, b = 1.86, odds ratio (OR) = 6.43) and especially on OD (P < 0.001, b = 3.92, OR = 50.57). Moreover, seven SNPs covering OPRK1 were examined in the majority of the above subjects (390 cases, including 327 AD, 177 CD and 97 OD subjects, and 358 controls). Although no significant differences in allele, genotype or haplotype frequency distributions were seen between cases and controls, a specific OPRK1 haplotype, GGCTTCT, was significantly associated with AD (v 2 = 8.12, d.f. = 1, P = 0.004). Logistic regression analyses also revealed its risk effect on AD (P = 0.009, b = 1.06, OR = 2.90). Population stratification artifact was not observed in the sample. Taken together, our findings supported a positive association between OPRD1 variants and SD, and a positive haplotypic association between OPRK1 and AD in EAs.

show abstract

Section: Introductionmentioning

confidence: 93%

The OPRD1 and OPRK1 loci in alcohol or drug dependence: OPRD1 variation modulates substance dependence risk

et al. 2007

View full text Add to dashboard Cite

show abstract

“…Data from 80 of these cases were reported in our previous study. 7 Detailed information about history of substance use was obtained by means of a structured interview administered by trained graduate-level research assistants. The mean age of the alcoholic sample was 46.9 ± 8.6 years and all but four cases were males.…”

Section: Subjectsmentioning

confidence: 99%

“…Because the endogenous opioid system plays a role in the reinforcing effects of a number of other drugs, we 7 previously investigated a functional coding polymorphism (+118A/G) within the reward-associatedopioid receptor gene (OPRM1) as a risk candidate for alcoholism in samples that were largely Caucasian. Our results supported the AA genotype and A allele as risk factors for alcoholism, with an odds ratio (OR) of 2.10 (Confidence Interval = 1.11-3.98) by genotype.…”

Section: Introductionmentioning

confidence: 99%

A functional polymorphism within the μ-opioid receptor gene and risk for abuse of alcohol and other substances

et al. 2002

View full text Add to dashboard Cite

Genetic association studies investigating the role of the +118A allele of the human -opioid receptor gene in risk for alcohol dependency have produced inconsistent findings, possibly because of the failure to recognize sampling methodology difficulties inherent in association studies of polygenic disorders. We examined the frequency of the AA genotype and A allele in several groups of substance-dependent cases, unrestricted controls, and super controls screened for the use of alcohol and cigarettes. Our findings and analyses suggest that the OPRM1 +118 polymorphism is a general risk gene for substance dependence, but is not specific to a particular substance. The nature of the conferred risk is likely to be in use of multiple substances, but it is not yet determined if the risk could be expressed in severity of use of any particular substance. The contribution of the gene to risk for substance dependence is small, and is detected most easily in studies that use control samples that are screened for all forms of substance dependence.

show abstract

“…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

552

399

View full text Add to dashboard Cite

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.

show abstract

Association of a functional ?-opioid receptor allele (+118A) with alcohol dependency

Cited by 90 publications

References 19 publications

The OPRD1 and OPRK1 loci in alcohol or drug dependence: OPRD1 variation modulates substance dependence risk

The OPRD1 and OPRK1 loci in alcohol or drug dependence: OPRD1 variation modulates substance dependence risk

A functional polymorphism within the μ-opioid receptor gene and risk for abuse of alcohol and other substances

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

Contact Info

Product

Resources

About