The A1 allele of the human D2 dopamine receptor gene is associated with increased activity of striatal L-amino acid decarboxylase in healthy subjects
The A1 allele of the human D2 dopamine receptor gene is associated with increased activity of striatal L-amino acid decarboxylase in healthy subjects
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DOI：
10.1097/01213011-200506000-00003
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发表时间：
2005-06-01
影响因子：
2.6
通讯作者：
Hietala, J
中科院分区：
文献类型：
--
作者：
Laakso, A;Pohjalainen, T;Hietala, J
人类多巴胺D2受体基因（DRD 2）的Taql限制性片段长度多态性（RFLP）的A1等位基因与纹状体中D2多巴胺受体的低密度相关。由于D2自身受体在调节多巴胺合成中的重要作用，我们的目的是检查具有A1等位基因的受试者是否改变了大脑中突触前多巴胺功能。我们还研究了其他两个DRD 2多态性，C957 T和-141C Ins/Del，这已被建议影响脑中D2受体水平的影响。使用正电子发射断层扫描和[F-18]氟多巴（[F-18]FDOPA）（多巴胺前体L-DOPA的放射性标记类似物）研究了33名健康芬兰志愿者的TaqIA RFLP、C957 T和-141 C Ins/Del多态性与纹状体多巴胺合成之间的关系。A1等位基因杂合子携带者（A1/A2; 10例受试者）的壳核[18 F]FDOPA摄取率显著高于无A1等位基因的受试者（A2/A2; 23例受试者）。C957 T和-141 C Ins/Del多态性对[F-18]FDOPA Ki值无显著影响。这些结果表明，A1等位基因的DRD 2基因与芳香族L-氨基酸脱羧酶，多巴胺的生物合成中的最终酶和微量胺（如β-苯乙胺）合成的限速酶的纹状体活性增加。这一发现可以通过较低的D2受体表达导致自身受体功能降低来解释，并表明A1等位基因携带者的脑中多巴胺和/或痕量胺合成速率增加。(c)2005年利平科特威廉姆斯&威尔金斯。
The A1 allele of the Taql restriction fragment length polymorphism (RFLP) of the human dopamine D2 receptor gene (DRD2) is associated with a low density of D2 dopamine receptors in the striatum. Because of the important role of D2 autoreceptors in regulating dopamine synthesis, we aimed to examine whether subjects with the A1 allele have altered presynaptic dopamine function in the brain. We also studied the effects of two other DRD2 polymorphisms, C957 T and - 141C Ins/Del, which have been suggested to affect D2 receptor levels in brain. The relationships between the TaqIA RFLP, C957T and - 141 C Ins/Del polymorphisms and striatal dopamine synthesis in 33 healthy Finnish volunteers were studied using positron emission tomography and [F-18]fluorodopa ([F-18]FDOPA), a radiolabelled analog of the dopamine precursor L-DOPA. Heterozygous carriers of the A1 allele (A1/A2; 10 subjects) had significantly higher (18%) [18F]FDOPA uptake in the putamen than subjects without the A1 allele (A2/A2; 23 subjects). C957T and - 141 C Ins/Del polymorphisms did not significantly affect [F-18]FDOPA Ki values. These results demonstrate that the A1 allele of DRD2 gene is associated with increased striatal activity of aromatic L-amino acid decarboxylase, the final enzyme in the biosynthesis of dopamine and the rate-limiting enzyme for trace amine (e.g. beta-phenylethyla mine) synthesis. The finding can be explained by lower D2 receptor expression leading to decreased autoreceptor function, and suggests that dopamine and/or trace amine synthesis rate is increased in the brains of Al allele carriers. (c) 2005 Lippincott Williams & Wilkins.