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No evidence of association between 118A>G OPRM1 polymorphism and heroin dependence in a large Bulgarian case-control sample.

ABSTRACT: The ?-opioid receptor is the primary site of action of most opioids. The 118A>G (rs1799971) polymorphism in exon 1 of the ?-opioid receptor gene (OPRM1) leads to an Asn40Asp amino acid change that affects a putative N-glycosylation site. It has been widely investigated for association with alcohol and drug dependence and pain sensitivity, with mixed results. The aim of the current study was to examine whether this polymorphism was associated with heroin dependence in a large Bulgarian cohort of 1842 active users and 1451 population controls. SNP genotyping was done using Real-Time PCR TaqMan technology. Association analyses were conducted, separately for Roma and non-Roma participants. Our results suggest that there is no direct effect of 118A>G genotype on the risk for heroin dependence among active heroin users.

SUBMITTER: Nikolov MA

PROVIDER: S-EPMC3128690 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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No evidence of association between 118A>G OPRM1 polymorphism and heroin dependence in a large Bulgarian case-control sample.

Nikolov Momchil A MA Beltcheva Olga O Galabova Antoaneta A Ljubenova Anna A Jankova Elena E Gergov Galin G Russev Atanas A AA Lynskey Michael T MT Nelson Elliot C EC Nesheva Eleonora E Krasteva Dorita D Lazarov Philip P Mitev Vanio I VI Kremensky Ivo M IM Kaneva Radka P RP Todorov Alexandre A AA

Drug and alcohol dependence 20110131 1

The μ-opioid receptor is the primary site of action of most opioids. The 118A>G (rs1799971) polymorphism in exon 1 of the μ-opioid receptor gene (OPRM1) leads to an Asn40Asp amino acid change that affects a putative N-glycosylation site. It has been widely investigated for association with alcohol and drug dependence and pain sensitivity, with mixed results. The aim of the current study was to examine whether this polymorphism was associated with heroin dependence in a large Bulgarian cohort of ...[more]

PMID: 21277709

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Project description:BACKGROUND:Genetic variability in ABCB1, encoding the P-glycoprotein efflux transporter, has been linked to altered methadone maintenance treatment dose requirements. However, subsequent studies have indicated that additional environmental or genetic factors may confound ABCB1 pharmacogenetics in different methadone maintenance treatment settings. There is evidence that genetic variability in OPRM1, encoding the mu opioid receptor, and ABCB1 may interact to affect morphine response in opposite ways. This study aimed to examine whether a similar gene-gene interaction occurs for methadone in methadone maintenance treatment. METHODS:Opioid-dependent subjects (n = 119) maintained on methadone (15-300 mg/day) were genotyped for five single nucleotide polymorphisms of ABCB1 (61A > G; 1199G > A; 1236C > T; 2677G > T; 3435C > T), as well as for the OPRM1 118A > G single nucleotide polymorphism. Subjects' methadone doses and trough plasma (R)-methadone concentrations (C(trough)) were compared between ABCB1 haplotypes (with and without controlling for OPRM1 genotype), and between OPRM1 genotypes (with and without controlling for ABCB1 haplotype). RESULTS:Among wild-type OPRM1 subjects, an ABCB1 variant haplotype group (subjects with a wild-type and 61A:1199G:1236C:2677T:3435T haplotype combination, or homozygous for the 61A:1199G:1236C:2677T:3435T haplotype) had significantly lower doses (median ± standard deviation 35 ± 5 versus 180 ± 65 mg/day, P < 0.01) and C(trough) (78 ± 22 versus 177 ± 97 ng/mL, P < 0.05) than ABCB1 wild-type subjects. Among subjects with the most common ABCB1 haplotype combination (wild-type with 61A:1199G:1236T:2677T:3435T), the OPRM1 118 A/G genotype was associated with a significantly higher C(trough) than 118 A/A (250 ± 126 versus 108 ± 36 ng/mL, P = 0.016). No ABCB1 haplotype group or OPRM1 genotype was associated with dose or C(trough) without taking into account confounding genetic variability at the other locus. Therefore, two interacting pharmacogenetic determinants of methadone maintenance treatment response were identified, ie, ABCB1, where variants are associated with lower methadone requirements, and OPRM1, where the variant is associated with higher methadone requirements. CONCLUSION:These opposing pharmacogenetic effects therefore need to be considered in combination when assessing methadone maintenance treatment pharmacogenetics.

Dataset Information

No evidence of association between 118A>G OPRM1 polymorphism and heroin dependence in a large Bulgarian case-control sample.

Publications

No evidence of association between 118A>G OPRM1 polymorphism and heroin dependence in a large Bulgarian case-control sample.

Similar Datasets

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