The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers
The A1 allele of the human D2 dopamine receptor gene predicts low D2 receptor availability in healthy volunteers
复制标题
DOI：
10.1038/sj.mp.4000350
复制
发表时间：
1998-05-01
影响因子：
11
通讯作者：
Hietala, J
中科院分区：
文献类型：
--
作者：
Pohjalainen, T;Rinne, JO;Hietala, J
正电子发射断层扫描（PET）研究显示，在人类纹状体多巴胺D-2受体密度在体内显着的个体差异。(1)已发现体内低D-2受体结合与酒精/物质依赖有关。（2-6）已表明，人D-2受体基因的A1等位基因可能与特定类型的酒精中毒有关（7），并可能与体外D-2受体密度降低有关。(8)我们使用PET和[C-11]雷氯必利测定了54名健康芬兰志愿者的D-2多巴胺受体结合密度（B-max）、亲和力（K-d）和可用性（B-max/K-d），以确定A1等位基因是否与体内D-2受体特征的“基线”差异相关。与A2/A2组相比，在A1/A2基因型组中观察到D-2受体可用性的统计学显著降低，反映了受体密度的改变。两组间的表观K-d无差异。总之，A1等位基因和低D-2受体的可用性在健康受试者之间的关联表明，A1等位基因的TaqIA多态性可能是在连锁不平衡的启动子/调节基因元件，影响多巴胺D-2受体的表达突变。这项研究提供了一个在体内的神经生物学相关的A1等位基因在健康志愿者。
Positron emission tomography (PET) studies have revealed significant interindividual variation in dopamine D-2 receptor density in vivo in human striatum.(1) Low D-2 receptor binding in vivo has been found to associate with alcohol/substance dependence,(2-6) It has been suggested that the Al allele of human D-2 receptor gene might be associated to a specific type of alcoholism(7) and possibly to a reduced D-2 receptor density in vitro.(8) We have determined D-2 dopamine receptor-binding density (B-max), affinity (K-d) and availability (B-max/K-d) in 54 healthy Finnish volunteers using PET and [C-11]raclopride in order to determine whether the A1 allele is associated with a 'baseline' difference in D-2 receptor characteristics in vivo. A statistically significant reduction in D-2 receptor availability reflecting an alteration in receptor density was observed in the A1/A2 genotype group compared to the A2/A2 group. There was no difference in apparent K-d between the two groups. In conclusion, the association between the A1 allele and low D-2 receptor availability in healthy subjects indicates that the A1 allele of the TaqIA polymorphism might be in linkage disequilibrium with a mutation in the promoter/regulatory gene element that affects dopamine D-2 receptor expression. This study provides an in vivo neurobiological correlate to the A1 allele in healthy volunteers.