Preliminary Evidence for cue-induced Alcohol Craving Modulated by Serotonin Transporter Gene Polymorphism rs1042173.
Preliminary Evidence for cue-induced Alcohol Craving Modulated by Serotonin Transporter Gene Polymorphism rs1042173.
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DOI：
10.3389/fpsyt.2012.00006
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发表时间：
2012
影响因子：
4.7
通讯作者：
Johnson BA
中科院分区：
文献类型：
--
作者：
Ait-Daoud N;Seneviratne C;Smith JB;Roache JD;Dawes MA;Liu L;Wang XQ;Johnson BA
我们以前已经表明，线索诱导的酒精渴望和倾向更高的饮酒调制SLC 6A 4与5-羟色胺转运体（5-HTT）表达水平的改变相关的等位基因差异。在一项独立研究中，我们描述了同一基因3′-非翻译区（3′-UTR）的另一个多态性，SNP rs 1042173，它也改变了5-HTT表达水平; rs 1042173的T等位基因与较低的mRNA和蛋白水平相关。在随后的分析中，发现TT基因型与高加索血统的酒精依赖（AD）个体的饮酒强度较高相关。基于这些发现，我们假设，低表达TT基因型与激烈的饮酒将预测更高的渴望酒精在AD个人。在这项初步研究中，我们试图通过检查34名西班牙裔AD志愿者（平均年龄34.8岁）的rs 1042173基因型[即，TT与TG/GG（Gx）]对酒精主观反应的差异。我们采用了人类实验室范式，并使用线性混合效应模型（SAS® PROC MIXED）分析数据，以评估治疗、提示程序和基因型主效应以及它们之间的双向相互作用效应。在主观“想喝”和“想喝”上，我们发现线索实验的主效应显著（p ≤ 0.01），基因型和线索效应之间存在交互效应（p < 0.05）。TT基因型与较高的冲动喝酒（p = 0.002）和渴望喝酒（p = 0.005）时，暴露于酒精线索。我们的研究结果不仅支持这一假设，即rs 1042173是一个遗传标记的提示诱导酒精渴求AD男性，但也提示了一个神经生物学机制与rs 1042173-TT基因型，触发不成比例的渴望响应酒精消费，这反过来可能会导致更激烈的饮酒。未来的研究需要更大的样本量来表征我们先前研究中报道的5-羟色胺转运蛋白连锁多态性区域（5′-HTTLPR）-L等位基因和rs 1042173-TT基因型对线索诱导的酒精渴求的交互作用。
We previously have shown that cue-induced alcohol craving and propensity for higher drinking are modulated by allelic differences in SLC6A4 associated with serotonin transporter (5-HTT) expression level alterations. In an independent study, we characterized another polymorphism, SNP rs1042173, in 3′-untranslated region (3′-UTR) of the same gene, which also altered 5-HTT expression levels; the T allele of rs1042173 was associated with lower mRNA and protein levels. In subsequent analyses, the TT genotype was found to be associated with higher drinking intensity in alcohol-dependent (AD) individuals of Caucasian descent. Building upon these findings, we hypothesized that the low-expressing TT genotype associated with intense drinking would predict higher craving for alcohol in AD individuals. In this pilot study, we sought to test our hypothesis by examining 34 Hispanic AD volunteers (mean age, 34.8 years) for rs1042173 genotype-based [i.e., TT versus TG/GG (Gx)] differences in subjective response to alcohol. We employed a human laboratory paradigm and analyzed the data using a linear mixed-effects model (SAS® PROC MIXED) to assess treatment, cue procedures, and genotype main effects as well as the two-way interaction effects between them. On subjective “urge to drink” and “crave for a drink,” we found a significant main effect of the cue experiment (p ≤ 0.01) and an interaction effect between genotype and cue effects (p < 0.05). TT genotype was associated with higher urge to drink (p = 0.002) and crave for a drink (p = 0.005) when exposed to alcohol cue. Our results not only support the hypothesis that rs1042173 is a genetic marker for cue-induced alcohol craving among AD males but also are suggestive of a neurobiological mechanism associated with the rs1042173-TT genotype that triggers a disproportionate craving in response to alcohol consumption, which in turn may lead to more intense drinking. Future studies with larger sample sizes are needed to characterize the interactive effects of the serotonin transporter-linked polymorphic region (5′-HTTLPR)-L-allele reported in our previous study and of the rs1042173-TT genotype on cue-induced alcohol craving.