Laboratory of the Biology of Addictive Diseases, Rockefeller University, New York, New York 10065, USA.
Ann N Y Acad Sci. 2010 Feb;1187:184-207. doi: 10.1111/j.1749-6632.2009.05275.x.
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.
成瘾和非法使用苯丙胺类兴奋剂是一种慢性、复发性的脑部疾病，如果不加以治疗，可能会导致严重的医疗、社会和经济问题。本文综述了近年来与阿片类药物和可卡因成瘾易感性相关的基因变异体研究的进展，主要集中在阿片类和单胺能系统的基因上。此外，我们提供了 PDYN 基因中顺式作用多态性和功能单体型的首个证据，海洛因成瘾者淋巴细胞中 OPRM1 基因的 DNA 甲基化率显著升高，以及阿片类药物维持治疗患者中 P 糖蛋白基因（ABCB1）三个单核苷酸多态性的基因型频率存在显著差异。在全基因组和多基因关联研究中，我们发现了几个新基因和已知基因的新变异与海洛因成瘾有关。最后，我们描述了一种新的技术的发展和应用：分子单体型分析技术，用于药物成瘾的遗传学研究。
