Vandenbergh D J, Rodriguez L A, Hivert E, Schiller J H, Villareal G, Pugh E W, Lachman H, Uhl G R
Molecular Neurobiology Branch, Intramural Research Program, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA.''
Am J Med Genet. 2000 Oct 9;96(5):678-83. doi: 10.1002/1096-8628(20001009)96:5<678::aid-ajmg15>3.0.co;2-8.
Substance abuse is a complex behavior that is caused by both environmental and genetic factors. Work to understand the genetic factors has focused on genes related to dopamine activity because of its critical role in rewarding and reinforcing behaviors. The DRD3 and other dopamine receptor subtypes are expressed in many areas of the limbic system, and have been the objects of study for their possible roles in several neuropsychiatric disorders. Interest in variants of the D4 gene was heightened by reports that some alleles were more frequent in individuals who score high on Novelty Seeking, an aspect of personality that may be related to drug seeking behavior. We now show that the long form of the DRD4 gene is more frequent in individuals with high quantity/frequency of drug use compared to controls (chi(2) = 5.7, df = 1, P = 0.017, odds ratio = 1.89, CI = 1.1-3.2). There is no difference in DRD3 allele frequencies in these samples, and there is no interaction of DRD4 alleles with those of the catecholamine-o-methyl- transferase gene (COMT) that we previously identified to be more frequent in substance abusers than controls [Vandenbergh, et al.: 1997: Am. J. Med. Gen. 74:439-442].
药物滥用是一种复杂行为，由环境和遗传因素共同导致。由于多巴胺在奖赏和强化行为中起关键作用，对遗传因素的研究工作聚焦于与多巴胺活性相关的基因。DRD3及其他多巴胺受体亚型在边缘系统的多个区域表达，并因其在几种神经精神疾病中可能发挥的作用而成为研究对象。一些报告称，某些等位基因在寻求新奇性得分高的个体中更为常见，寻求新奇性是人格的一个方面，可能与药物寻求行为有关，这使得人们对D4基因的变体兴趣大增。我们现在发现，与对照组相比，DRD4基因的长型在药物使用量/频率高的个体中更为常见（卡方 = 5.7，自由度 = 1，P = 0.017，优势比 = 1.89，置信区间 = 1.1 - 3.2）。在这些样本中，DRD3等位基因频率没有差异，并且DRD4等位基因与我们之前发现的在药物滥用者中比对照组更常见的儿茶酚-O-甲基转移酶基因（COMT）的等位基因之间没有相互作用[范登伯格等人：1997年：《美国医学遗传学杂志》74：439 - 442]。
