Abstract
Addiction to opiates and illicit use of psychostimulants is a chronic, relapsing brain disease that, if left untreated, can cause major medical, social, and economic problems. This article reviews recent progress in studies of association of gene variants with vulnerability to develop opiate and cocaine addictions, focusing primarily on genes of the opioid and monoaminergic systems. In addition, we provide the first evidence of a cis-acting polymorphism and a functional haplotype in the PDYN gene, of significantly higher DNA methylation rate of the OPRM1 gene in the lymphocytes of heroin addicts, and significant differences in genotype frequencies of three single-nucleotide polymorphisms of the P-glycoprotein gene (ABCB1) between "higher" and "lower" methadone doses in methadone-maintained patients. In genomewide and multigene association studies, we found association of several new genes and new variants of known genes with heroin addiction. Finally, we describe the development and application of a novel technique: molecular haplotyping for studies in genetics of drug addiction.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics
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Catechol O-Methyltransferase / genetics
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Cocaine-Related Disorders / genetics*
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Cocaine-Related Disorders / therapy
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Enkephalins / genetics
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Epigenesis, Genetic
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Genetic Markers
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Genetic Variation*
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Genome-Wide Association Study
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Haplotypes
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Humans
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Methadone / metabolism
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Methadone / therapeutic use
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Opioid-Related Disorders / genetics*
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Opioid-Related Disorders / therapy
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Pharmacogenetics
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Protein Precursors / genetics
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Receptor, Melanocortin, Type 2 / genetics
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Receptor, Serotonin, 5-HT1B / genetics
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Receptors, Opioid, kappa / genetics
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Receptors, Opioid, mu / genetics
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Tryptophan Hydroxylase / genetics
Substances
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ABCB1 protein, human
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Enkephalins
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Genetic Markers
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HTR1B protein, human
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Protein Precursors
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Receptor, Melanocortin, Type 2
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Receptor, Serotonin, 5-HT1B
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Receptors, Opioid, kappa
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Receptors, Opioid, mu
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preproenkephalin
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Tryptophan Hydroxylase
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Catechol O-Methyltransferase
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Methadone