Hospital for Psychiatry and Psychotherapy, Ernst Moritz Arndt University Greifswald, Germany.
Prog Neuropsychopharmacol Biol Psychiatry. 2010 Feb 1;34(1):45-9. doi: 10.1016/j.pnpbp.2009.08.024. Epub 2009 Sep 29.
D(2) receptor function can be assessed by growth hormone (GH) response to apomorphine. Several association studies between dopamine receptor polymorphisms and results of the apomorphine challenge test with normal and alcohol-dependent subjects yielded inconsistent results. In this pilot study, we tested polymorphisms from the DRD2 region for GH response to apomorphine challenge in more detail.
Apomorphine challenge tests measuring GH responses on 5 time points were performed on day 1 of alcohol detoxification in 43 patients with alcohol dependence; patients were genotyped for 11 polymorphisms including DRD2, ANKK1, NCAM1 and TTC12.
Associations (p<0.05) were found for ANKK1 (rs11604671, rs1800497) and DRD2 (rs6276, rs1076560), which are located on adjacent chromosomal positions. Consistent with PET studies suggesting a reduced D(2) receptor availability in patients carrying the ANKK1 rs1800497 T polymorphism (formerly known as DRD2 TaqI A1) we found a reduced GH response to apomorphine in those subjects.
This has been the first study showing significant associations between apomorphine-induced GH response and SNPs in DRD2 and ANKK1 in alcohol-dependent patients. In this respect, our preliminary results are in line with other reports which suggested that DRD2 and ANKK1 polymorphisms influence D(2) receptor availability and signal transduction in the dopaminergic pathways. Small sample size in our study limits the generalizability of our results.
D2 受体功能可以通过生长激素（GH）对阿朴吗啡的反应来评估。几项多巴胺受体多态性与正常和酒精依赖受试者的阿朴吗啡挑战试验结果之间的关联研究得出了不一致的结果。在这项初步研究中，我们更详细地测试了 DRD2 区域的多态性与阿朴吗啡挑战试验中 GH 反应的关系。
在 43 名酒精依赖患者的酒精戒断第 1 天，进行了 5 个时间点的阿朴吗啡挑战试验，以测量 GH 反应；患者被分为 11 个多态性，包括 DRD2、ANKK1、NCAM1 和 TTC12。
ANKK1(rs11604671, rs1800497)和 DRD2(rs6276, rs1076560)的多态性与 GH 对阿朴吗啡的反应有关，它们位于相邻的染色体位置。与 PET 研究一致，提示携带 ANKK1 rs1800497 T 多态性（以前称为 DRD2 TaqI A1）的患者 D2 受体可用性降低，我们发现这些患者对阿朴吗啡的 GH 反应降低。
这是第一项表明酒精依赖患者阿朴吗啡诱导的 GH 反应与 DRD2 和 ANKK1 中的 SNPs 之间存在显著关联的研究。在这方面，我们的初步结果与其他报告一致，表明 DRD2 和 ANKK1 多态性影响多巴胺能途径中 D2 受体的可用性和信号转导。我们研究中的小样本量限制了我们结果的普遍性。
