Leventhal Adam M, Kirkpatrick Matthew G, Pester Mollie S, McGeary John E, Swift Robert M, Sussman Steve, Kahler Christopher W
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, 2250 Alcazar Street, CSC 240, Los Angeles, 90033, CA, USA.
Department of Psychology, Dornsife College of Letters, Arts, and Sciences, University of Southern California, Los Angeles, CA, USA.
Psychopharmacology (Berl). 2017 Jan;234(2):307-315. doi: 10.1007/s00213-016-4462-z. Epub 2016 Oct 22.
A previous genome-wide association study (GWAS) in a predominately Caucasian sample of healthy young adults linked greater amphetamine-induced rewarding effects with the rs3784943 G allele of the cadherin 13 (CDH13; i.e., a cell adhesion molecule implicated in neuronal connectivity) gene. This association has not been subsequently examined, nor has it been studied in Asian populations, which may have greater frequencies of the risk allele.
The objective of this study was to examine the association of rs3784943 with amphetamine response in a racially heterogeneous sample (37 % Asian) of healthy young adults.
Participants (N = 84; 18-35 years old) genotyped for rs3784943 completed counterbalanced sessions involving 20 mg oral d-amphetamine or placebo administration. At both sessions, cardiovascular and subjective drug effects measures were collected.
In the combined racially heterogeneous sample, amphetamine (vs. placebo) effects were significantly greater on "Feel Drug" ratings (p < 0.05) and marginally greater on "Feel High" ratings and systolic blood pressure (p < 0.10) in G/A + G/G genotypes than A/A genotypes. The G allele was more common among Asian than other racial groups. Among the subsample of Asian participants (N = 31), drug effects were significantly greater on Feel Drug (p < 0.05) and marginally greater on Feel High and heart rate (p < 0.10) among Asians with G/A + G/G (vs. A/A) genotypes.
In concert with a previous GWAS result, this candidate gene study provides convergent evidence implicating CDH13 rs3784943 variant in d-amphetamine's drug effect profile and suggests generalization to Asian populations. CDH13 and genes coding for other cell adhesion molecules may be worthy of study in the biology of psychostimulant abuse liability.
先前一项针对健康年轻成年人的全基因组关联研究（GWAS），该研究主要以白种人为样本，结果表明，钙黏蛋白13（CDH13，一种与神经元连接有关的细胞黏附分子）基因的rs3784943 G等位基因与苯丙胺诱导的更强奖赏效应有关。此关联随后未再被研究，在亚洲人群中也未被研究过，而亚洲人群中该风险等位基因的频率可能更高。
本研究的目的是在一个种族异质性样本（37%为亚洲人）的健康年轻成年人中，研究rs3784943与苯丙胺反应之间的关联。
对rs3784943进行基因分型的参与者（N = 84；年龄在18 - 35岁之间）完成了平衡试验，涉及口服20毫克右旋苯丙胺或安慰剂。在两个试验阶段，均收集了心血管和主观药物效应指标。
在合并的种族异质性样本中，与A/A基因型相比，G/A + G/G基因型对“感觉药物”评分的苯丙胺（与安慰剂相比）效应显著更大（p < 0.05），对“感觉兴奋”评分和收缩压的效应略大（p < 0.10）。G等位基因在亚洲人中比在其他种族群体中更常见。在亚洲参与者子样本（N = 31）中，G/A + G/G（与A/A）基因型的亚洲人在“感觉药物”方面的药物效应显著更大（p < 0.05），在“感觉兴奋”和心率方面的效应略大（p < 0.10）。
与先前的GWAS结果一致，这项候选基因研究提供了趋同证据，表明CDH13 rs3784943变体与右旋苯丙胺的药物效应特征有关，并表明该关联可推广至亚洲人群。CDH13以及编码其他细胞黏附分子的基因可能在精神兴奋剂滥用易感性生物学方面值得研究。
