Eirich Antonia, Biermann Teresa, Müller Christian P, Kornhuber Johannes, Benyamin Beben, Hulse Gary K, Wildenauer Dieter B, Schwab Sibylle G
Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
School of Health Sciences, Australian Centre for Precision Health, University of South Australia Cancer Research Institute, University of South Australia, Adelaide, South Australia.
Psychiatr Genet. 2019 Feb;29(1):18-25. doi: 10.1097/YPG.0000000000000208.
Susceptibility to heroin dependence is strongly influenced by genetic factors with heritability estimates as high as 0.7. A number of genes, as well as environmental factors, are likely to contribute to its etiology. Not all individuals who have ever tried heroin at some stage during their lifetime become dependent on heroin. It has been suggested that genetic factors might be more important in the transition stage to heroin dependence rather than in environmental exposures and experimenting with heroin. As the features of substance dependence and memory formation have been found to be strikingly similar, we have focused on a key enzyme involved in long-term potentiation and synaptic plasticity, namely the calcium-dependent/calmodulin-dependent protein kinase IIα (CAMKIIa). We hypothesized, that CamK2A genetic variation may play a role in the transition from occasional to regular heroin use.
Using quantitative trait association analysis, we addressed this hypothesis by correlating the self-reported time interval between occasional and regular heroin use with the frequency of 12 single nucleotide polymorphisms located within the genomic region of the CamK2A gene. A sample of 570 Caucasian patients was available for analysis.
Single marker association analysis (rs10066581, P=0.007), as well as haplotype analysis (global P=0.005), suggested an association with the quantitative trait 'time interval from occasional to regular heroin use.'
Our results propose that genetic variants located in the genomic region of the CamK2A gene may be involved in transition time from occasional to regular heroin use.
海洛因依赖易感性受遗传因素的强烈影响,遗传度估计高达0.7。许多基因以及环境因素可能都对其病因有影响。并非所有在人生某个阶段尝试过海洛因的个体都会对海洛因产生依赖。有人提出,在向海洛因依赖转变的阶段,遗传因素可能比环境暴露和尝试使用海洛因更为重要。由于已发现物质依赖和记忆形成的特征极为相似,我们聚焦于一种参与长时程增强和突触可塑性的关键酶,即钙/钙调蛋白依赖性蛋白激酶IIα(CAMKIIa)。我们推测,CamK2A基因变异可能在从偶尔使用海洛因转变为经常使用海洛因的过程中发挥作用。
我们采用数量性状关联分析,通过将自我报告的偶尔使用海洛因与经常使用海洛因之间的时间间隔,与位于CamK2A基因基因组区域内的12个单核苷酸多态性的频率进行关联,来验证这一假设。有570名白种人患者样本可供分析。
单标记关联分析(rs10066581,P = 0.007)以及单倍型分析(全局P = 0.005)表明,与“从偶尔使用海洛因转变为经常使用海洛因的时间间隔”这一数量性状存在关联。
我们的结果表明,位于CamK2A基因基因组区域的遗传变异可能参与了从偶尔使用海洛因到经常使用海洛因的转变时间。