Department and Institute of Psychiatry (LIM 23), University of São Paulo Medical School, São Paulo, SP, Brazil ; Laboratory of Genetics and Molecular Cardiology (LIM 13), Heart Institute-InCor, University of São Paulo Medical School, São Paulo, SP, Brazil.
PLoS One. 2013 Nov 27;8(11):e80505. doi: 10.1371/journal.pone.0080505. eCollection 2013.
The search for genetic vulnerability factors in cocaine dependence has focused on the role that neuroplasticity plays in addiction. However, like many other drugs, the ability of an individual to metabolize cocaine can also influence susceptibility to dependence. Butyrylcholinesterase (BChE) metabolizes cocaine, and genetic variants of the BChE gene (BCHE) alter its catalytic activity. Therefore, we hypothesize that cocaine users with polymorphisms in BCHE can show diverse addictive behaviors due to differences in effective plasma concentrations of cocaine. Those polymorphisms might also influence users to prefer one of the two main preparations (crack or powder cocaine), despite having equal access to both. The present work investigates polymorphisms in BCHE and if those genetic variants constitute risk factors for cocaine dependence and for crack cocaine use.
A total of 1,436 individuals (698 cocaine-dependent patients and 738 controls) were genotyped for three single nucleotide polymorphisms (SNPs) in BCHE: rs1803274, rs4263329, and rs4680662.
For rs4263329, a nominal difference was found between cases and controls. For rs1803274 (the functional SNP), a statistically significant difference was found between patients who used crack cocaine exclusively and those who used only powder cocaine (P = 0.027; OR = 4.36; 95% CI = 1.18-16.04). Allele frequencies and genotypes related to other markers did not differ between cases and controls or between the two cocaine subgroups.
Our findings suggest that the AA genotype of rs1803274 is a risk factor for crack cocaine use, which is more addictive than powder cocaine use. Further studies are needed in order to confirm this preliminary result and clarify the role of BCHE and its variants in cocaine dependence.
在可卡因依赖的遗传易感性因素的研究中，神经可塑性的作用受到了广泛关注。然而，与许多其他药物一样，个体代谢可卡因的能力也会影响其对依赖的易感性。丁酰胆碱酯酶（BChE）代谢可卡因，而 BChE 基因（BCHE）的遗传变异会改变其催化活性。因此，我们假设 BCHE 基因多态性的可卡因使用者可能由于可卡因的有效血浆浓度的差异而表现出不同的成瘾行为。这些多态性也可能影响使用者偏爱两种主要制剂（快克或粉末可卡因）中的一种，尽管他们可以平等地获得这两种制剂。本研究调查了 BCHE 中的多态性，以及这些遗传变异是否构成可卡因依赖和快克可卡因使用的危险因素。
共对 1436 名个体（698 名可卡因依赖患者和 738 名对照）进行了 BCHE 中的三个单核苷酸多态性（SNP）的基因分型：rs1803274、rs4263329 和 rs4680662。
对于 rs4263329，病例组和对照组之间存在显著差异。对于 rs1803274（功能 SNP），仅使用快克可卡因的患者与仅使用粉末可卡因的患者之间存在统计学差异（P = 0.027；OR = 4.36；95% CI = 1.18-16.04）。与其他标记物相关的等位基因频率和基因型在病例组和对照组之间或在两个可卡因亚组之间没有差异。
我们的研究结果表明，rs1803274 的 AA 基因型是使用快克可卡因的危险因素，其成瘾性高于使用粉末可卡因。需要进一步的研究来证实这一初步结果，并阐明 BCHE 及其变体在可卡因依赖中的作用。
