Noble E P, Blum K, Ritchie T, Montgomery A, Sheridan P J
Neuropsychiatric Institute, UCLA 90024.
Arch Gen Psychiatry. 1991 Jul;48(7):648-54. doi: 10.1001/archpsyc.1991.01810310066012.
The allelic association of the human D2 dopamine receptor gene with the binding characteristics of the D2 dopamine receptor was determined in 66 brains of alcoholic and non-alcoholic subjects. In a blinded experiment, DNA from the cerebral cortex was treated with the restriction endonuclease Taql and probed with a 1.5-kilobase (kb) digest of a clone (lambda hD2G1) of the human D2 dopamine receptor gene. The binding characteristics (Kd [binding affinity] and Bmax [number of binding sites]) of the D2 dopamine receptor were determined in the caudate nuclei of these brains using tritiated spiperone as the ligand. The adjusted Kd was significantly lower in alcoholic than in nonalcoholic subjects. In subjects with the A1 allele, in whom a high association with alcoholism was found, the Bmax was significantly reduced compared with the Bmax of subjects with the A2 allele. Moreover, a progressively reduced Bmax was found in subjects with A2/A2, A1/A2, and A1/A1 alleles, with subjects with A2/A2 having the highest mean values, and subjects with A1/A1, the lowest. The polymorphic pattern of the D2 dopamine receptor gene and its differential expression of receptors suggests the involvement of the dopaminergic system in conferring susceptibility to at least one subtype of severe alcoholism.
在66名酗酒者和非酗酒者的大脑中，研究了人类D2多巴胺受体基因的等位基因与D2多巴胺受体结合特性之间的关联。在一项盲法实验中，用限制性内切酶TaqI处理大脑皮质的DNA，并用人类D2多巴胺受体基因克隆（λhD2G1）的1.5千碱基（kb）消化片段进行探测。以氚化螺哌隆作为配体，在这些大脑的尾状核中测定D2多巴胺受体的结合特性（Kd[结合亲和力]和Bmax[结合位点数量]）。酗酒者的调整后Kd显著低于非酗酒者。在与酒精中毒高度相关的A1等位基因携带者中，其Bmax与A2等位基因携带者相比显著降低。此外，在A2/A2、A1/A2和A1/A1等位基因携带者中发现Bmax逐渐降低，其中A2/A2携带者的平均值最高，A1/A1携带者的平均值最低。D2多巴胺受体基因的多态性模式及其受体的差异表达表明，多巴胺能系统参与了至少一种严重酒精中毒亚型易感性的形成。
