Persico A M, O'Hara B F, Farmer S, Gysin R, Flanagan S D, Uhl G R
National Institute on Drug Abuse, Addiction Research Center, Johns Hopkins University School of Medicine, Baltimore, MD.
Drug Alcohol Depend. 1993 Feb;31(3):229-34. doi: 10.1016/0376-8716(93)90005-b.
The D2 dopamine receptor gene (DRD2) displays Taq I restriction fragment length polymorphisms (RFLPs) at two different loci, termed A and B. One of the three different Taq I A 'alleles' described at this site, the A1 allele (size = 6.6 kb), has been found to be associated with alcoholism and with drug abuse in the majority of studies reported to date. A complete map of the Taq I A RFLP site has been constructed, through hybridization with different fragments of the 3' flanking region and polymerase chain reaction (PCR). When screening 432 unrelated individuals to establish possible A1 allelic association with drug abuse or dependence, we have encountered a novel Taq I A RFLP, which we have named 'A4' (size = 8.6 kb). This sequence variant displays a frequency of approximately 1% in our sample and shows a Mendelizing genetic pattern in an Italian nuclear family. Primers suitable for detecting A4 using PCR have been designed. The A4, but not the A3 'allele', displays substantial overlap with the A1. In particular, A2 and A3 share the presence of a Taq I restriction site, whose absence in A1 and A4 is apparently associated with substance abuse vulnerability. Therefore, in association studies it is proper to contrast individuals displaying A1 and A4 RFLP patterns, with individuals displaying A2 and A3 RFLPs.
D2多巴胺受体基因（DRD2）在两个不同位点呈现Taq I限制性片段长度多态性（RFLP），分别称为A和B。在该位点描述的三种不同的Taq I A“等位基因”中，A1等位基因（大小 = 6.6 kb），在迄今为止报道的大多数研究中已发现其与酒精中毒和药物滥用有关。通过与3'侧翼区域的不同片段杂交和聚合酶链反应（PCR），构建了Taq I A RFLP位点完整图谱。在筛查432名无亲缘关系个体以确定A1等位基因与药物滥用或依赖的可能关联时，我们遇到了一种新的Taq I A RFLP，我们将其命名为“A4”（大小 = 8.6 kb）。该序列变异在我们的样本中频率约为1%，并在一个意大利核心家庭中呈现孟德尔遗传模式。已设计出适合用PCR检测A4的引物。A4而非A3“等位基因”与A1有大量重叠。特别是，A2和A3共享一个Taq I限制性位点，而A1和A4中该位点缺失，这显然与物质滥用易感性有关。因此，在关联研究中，将呈现A1和A4 RFLP模式的个体与呈现A2和A3 RFLP的个体进行对比是合适的。
