Gelernter J, Kranzler H, Coccaro E, Siever L, New A, Mulgrew C L
Psychiatry 116A2, VA Connecticut Healthcare System, West Haven Campus, West Haven, CT 06516, USA.
Am J Hum Genet. 1997 Nov;61(5):1144-52. doi: 10.1086/301595.
Two reports have been published suggesting an association between the personality trait of novelty seeking and the DRD47R allele at the D4 dopamine-receptor locus (with heterozygotes or homozygotes for DRD47R having higher novelty seeking). We studied novelty seeking and four coding-sequence polymorphisms affecting protein structure in the D4 dopamine-receptor gene (DRD4) in a sample of 341 American subjects, of whom 224 are of primarily European ancestry and 117 are of primarily African ancestry. These subjects had diagnoses of substance dependence or personality disorder (PD) or were screened to exclude major psychiatric diagnosis. We found that, although the substance-dependent subjects had significantly higher novelty seeking than the control and PD subjects, they did not differ in DRD47R allele frequency. There was no association between any DRD4 polymorphism and novelty seeking in any population or diagnostic group, except for a significant association between the DRD47R allele and lower novelty seeking among European American females and African American substance abusers. The novelty seeking of subjects heterozygous for a null mutation did not differ from that of subjects with two functional alleles. We conclude that the most likely explanation of these results is that the DRD4 VNTR does not influence directly the trait of novelty seeking, in these samples.
已有两篇报道指出，寻求新奇这一个性特质与位于多巴胺D4受体基因座的DRD47R等位基因之间存在关联（DRD47R的杂合子或纯合子具有更高的寻求新奇水平）。我们在341名美国受试者中研究了寻求新奇以及影响多巴胺D4受体基因（DRD4）蛋白质结构的四种编码序列多态性，其中224人主要为欧洲血统，117人主要为非洲血统。这些受试者被诊断为物质依赖或人格障碍（PD），或者经过筛查以排除主要的精神疾病诊断。我们发现，虽然物质依赖受试者的寻求新奇水平显著高于对照组和PD受试者，但他们在DRD47R等位基因频率上并无差异。在任何人群或诊断组中，任何DRD4多态性与寻求新奇之间均无关联，但在欧美女性和非裔美国药物滥用者中，DRD47R等位基因与较低的寻求新奇水平之间存在显著关联。无功能突变杂合子受试者的寻求新奇水平与具有两个功能等位基因的受试者并无差异。我们得出结论，在这些样本中，对这些结果最可能的解释是DRD4可变数目串联重复序列（VNTR）并不直接影响寻求新奇这一个性特质。
