Noble E P, Blum K, Khalsa M E, Ritchie T, Montgomery A, Wood R C, Fitch R J, Ozkaragoz T, Sheridan P J, Anglin M D
Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles.
Drug Alcohol Depend. 1993 Oct;33(3):271-85. doi: 10.1016/0376-8716(93)90113-5.
The objective of the present study was to examine allelic prevalence of the D2 dopamine receptor (DRD2) gene in male cocaine-dependent (CD) Caucasian (non-Hispanic) subjects and to determine the relationship of DRD2 alleles to family history and selected behavioral measures. The prevalence of the A1 allele in CD subjects (n = 53) was 50.9%. It was significantly higher than either the 16.0% prevalence (P < 10(-4)) in non-substance abusing controls (n = 100) or the 30.9% prevalence (P < 10(-2)) in population controls (n = 265) wherein substance abusers were not excluded. Similarly, a significantly higher prevalence (P < 10(-2)) of the B1 allele was found in CD subjects (n = 52) compared with non-substance abusing controls (n = 53); 38.5% vs. 13.2%. Logistic regression analysis of CD subjects identified potent routes of cocaine use and the interaction of early deviant behaviors and parental alcoholism as significant risk factors associated with the A1 allele. The cumulative number of these three risk factors in CD subjects was positively and significantly (P < 10(-3)) related to A1 allelic prevalence. The data showing a strong association of the minor alleles (A1 and B1) of the DRD2 with cocaine dependence suggest that a gene, located on the q22-q23 region of chromosome 11, confers susceptibility to this drug disorder.
本研究的目的是检测男性可卡因依赖（CD）的高加索（非西班牙裔）受试者中D2多巴胺受体（DRD2）基因的等位基因流行情况，并确定DRD2等位基因与家族史及选定行为指标之间的关系。CD受试者（n = 53）中A1等位基因的流行率为50.9%。该流行率显著高于非物质滥用对照组（n = 100）中的16.0%（P < 10⁻⁴）或总体对照组（n = 265，未排除物质滥用者）中的30.9%（P < 10⁻²）。同样，与非物质滥用对照组（n = 53）相比，CD受试者（n = 52）中B1等位基因的流行率显著更高（P < 10⁻²）；分别为38.5%和13.2%。对CD受试者进行的逻辑回归分析确定，可卡因使用的有效途径以及早期异常行为与父母酗酒的相互作用是与A1等位基因相关的显著危险因素。CD受试者中这三个危险因素的累积数量与A1等位基因流行率呈正相关且具有显著性（P < 10⁻³）。数据显示DRD2的次要等位基因（A1和B1）与可卡因依赖之间存在强关联，这表明位于11号染色体q22 - q23区域的一个基因赋予了对这种药物紊乱的易感性。
