Supplementary Material for: <b><i>TPH1</i></b> and <b><i>5-HTTLPR</i></b> Genes Specifically Interact in Opiate Dependence but Not in Alcohol Dependence
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<b><i>Background:</i></b> Different drug dependencies may have unique genetic vulnerabilities. Changes in serotonin availability and function have been linked to addiction. We investigated whether 2 serotonergic polymorphisms, <i>TPH1 A218C</i> (rs1800532) and <i>5-HTT</i>-linked promoter region <i>(5-HTTLPR)</i> (rs25531), are differently associated with alcohol or opiate dependence. <b><i>Methods:</i></b> Alcohol-dependent patients (n = 292), opiate-dependent patients (n = 309), and healthy controls (n = 301) were recruited from the Han Chinese population in Taiwan. Genotypes of <i>TPH1 A218C</i> and <i>5-HTTLPR</i> polymorphisms were analyzed using a polymerase chain reaction with restriction fragment length polymorphism. <b><i>Results:</i></b> The genotype frequencies of the <i>TPH1 A218C</i> polymorphisms were not significantly different in the 3 groups. The genotype frequencies of the<i> 5-HTTLPR S+</i> (<i>S/S</i>,<i> S/L</i><sub><i>G</i></sub>,<i> L</i><sub><i>G</i></sub><i>/L</i><sub><i>G</i></sub>) polymorphisms were significantly higher in opiate-dependent patients (χ<sup>2</sup> = 8.77, p = 0.01), but not after controlling for the covariates of age, gender, and interaction effect in logistic regression analysis. Moreover, there was a significant interaction between the <i>TPH1 A218C A/C</i> and <i>5-HTTLPR S+</i> gene polymorphisms in opiate-dependent (OR 2.72, p = 0.01), but not in alcohol-dependent patients. <b><i>Conclusions:</i></b> Our data suggested that there may be a differential genetic vulnerability in serotonergic genes for alcohol and opiate addiction. However, replications of our findings are still needed.
**研究背景**：不同类型的药物依赖可能存在独特的遗传易感性。5-羟色胺（serotonin）的可获得性与功能变化已被证实与成瘾行为相关。本研究旨在探究两种5-羟色胺能基因多态性——色氨酸羟化酶1（TPH1）A218C（rs1800532）与5-羟色胺转运体（5-HTT）连接启动子区域（5-HTTLPR）（rs25531）——是否与酒精依赖或阿片类药物依赖存在不同的关联。 **研究方法**：本研究从中国台湾汉族人群中招募了酒精依赖患者（n=292）、阿片类药物依赖患者（n=309）以及健康对照者（n=301）。采用聚合酶链式反应-限制性片段长度多态性（polymerase chain reaction-restriction fragment length polymorphism, PCR-RFLP）技术，对TPH1 A218C与5-HTTLPR基因多态性的基因型进行检测分析。 **研究结果**：TPH1 A218C基因多态性的基因型频率在三组人群中均无显著差异。5-HTTLPR S+（包括S/S、S/LG、LG/LG）基因型的频率在阿片类药物依赖患者中显著更高（χ²=8.77，p=0.01），但在对年龄、性别作为协变量，并校正交互效应进行逻辑回归分析后，该差异不再显著。此外，在阿片类药物依赖患者中，TPH1 A218C A/C与5-HTTLPR S+基因多态性之间存在显著的交互作用（比值比OR=2.72，p=0.01），但在酒精依赖患者中未观察到该交互效应。 **研究结论**：本研究数据提示，酒精成瘾与阿片类药物成瘾的5-羟色胺能基因遗传易感性可能存在差异。但本研究结果仍需进一步的重复验证。
