Lobos E A, Todd R D
Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Am J Med Genet. 1998 Sep 7;81(5):411-9.
Previous studies testing the dopamine D2 receptor (DRD2) locus for association with alcoholism have produced conflicting results. Failure to screen controls for substance abuse and failure to assess alcoholics for severity have been proposed as causes for the inability of some studies to detect an association. We have reevaluated the involvement of DRD2 mutations in susceptibility to alcoholism with a cladistics-based association analysis after restricting an alcoholic sample to more severe cases. For the present study we tested 55 alcoholic probands and 80 normal controls for differences in the frequency of six haplotypes at the DRD2 locus. The haplotypes were derived from five di-allelic polymorphisms spanning all but the first exon of the DRD2 gene. A cladogram constructed from the haplotypes provided the evolutionary context for a nested statistical analysis. We found no significant evidence for association of the DRD2 haplotypes analyzed with the more severe alcoholic phenotype.
以往针对多巴胺D2受体（DRD2）基因座与酒精中毒关联性的研究结果相互矛盾。一些研究未能检测到关联性，原因可能是未对对照组进行药物滥用筛查，以及未对酗酒者的严重程度进行评估。我们在将酗酒样本限定为病情更严重的病例后，通过基于分支系统学的关联分析，重新评估了DRD2突变在酒精中毒易感性中的作用。在本研究中，我们检测了55名酗酒先证者和80名正常对照者DRD2基因座上六种单倍型的频率差异。这些单倍型来自五个双等位基因多态性，涵盖了DRD2基因除第一个外显子之外的所有区域。根据这些单倍型构建的分支图为嵌套统计分析提供了进化背景。我们没有发现所分析的DRD2单倍型与更严重酗酒表型之间存在显著关联的证据。
