Heroin dependence is a complex disease with multiple phenotypes. Classification of heroin users into more homogeneous subgroups on the basis of these phenotypes could help to identify the involved genetic factors and precise treatments. This study aimed to identify the association between genetic polymorphisms of DA synthesis and metabolism genes, including tyrosine hydroxylase (TH), DOPA decarboxylase (DDC), solute carrier family 6 member 3 (SLC6A3) and DA beta-hydroxylase (DBH), with six important phenotypes of heroin dependence. A total of 801 heroin dependent patients were recruited and fourteen potential functional single nucleotide polymorphisms (SNPs) were genotyped by SNaPshot. Associations between SNPs with six phenotypes were mainly assessed by binary logistic regression. Generalized multifactor dimensionality reduction was used to analyze the gene-by-gene and gene-by-environment interactions. We found that DBH rs1611114 TT genotype had a protective effect on memory impairment after heroin dependence (P = 0.002, OR = 0.610). We also found that the income-rs12666409-rs129915-rs1611114 interaction yielded the highest testing balance accuracy and cross-validation consistency for memory change after heroin dependence. Our results suggest that the memory change after heroin dependence was a result of a combination of genetics and environment. This finding could lead to a better understanding of heroin dependence and further improve personalized treatment.

中文翻译：

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多巴胺合成和代谢基因与海洛因依赖的多种表型的关联研究。

海洛因依赖是一种具有多种表型的复杂疾病。在这些表型的基础上，将海洛因使用者分类为更均一的亚组可以帮助确定涉及的遗传因素和精确的治疗方法。这项研究旨在确定DA合成和代谢基因的遗传多态性之间的关联，包括酪氨酸羟化酶（TH），DOPA脱羧酶（DDC），溶质载体家族6成员3（SLC6A3）和DAβ-羟化酶（DBH），其中六个海洛因依赖的重要表型。总共招募了801名海洛因依赖患者，并通过SNaPshot对14种潜在的功能性单核苷酸多态性（SNP）进行了基因分型。具有六种表型的SNP之间的关联主要通过二元logistic回归进行评估。广义多维度降维用于分析基因之间的相互作用和基因之间的相互作用。我们发现DBH rs1611114 TT基因型对海洛因依赖后的记忆障碍有保护作用（P = 0.002，OR = 0.610）。我们还发现，收入-rs12666409-rs129915-rs1611114交互对于海洛因依赖后的记忆变化产生了最高的测试平衡准确性和交叉验证一致性。我们的结果表明，海洛因依赖后的记忆变化是遗传和环境相结合的结果。这一发现可能导致对海洛因依赖性的更好理解，并进一步改善个性化治疗。我们发现DBH rs1611114 TT基因型对海洛因依赖后的记忆障碍有保护作用（P = 0.002，OR = 0.610）。我们还发现，收入-rs12666409-rs129915-rs1611114交互对于海洛因依赖后的记忆变化产生了最高的测试平衡准确性和交叉验证一致性。我们的结果表明，海洛因依赖后的记忆变化是遗传和环境相结合的结果。这一发现可能导致对海洛因依赖性的更好理解，并进一步改善个性化治疗。我们发现DBH rs1611114 TT基因型对海洛因依赖后的记忆障碍有保护作用（P = 0.002，OR = 0.610）。我们还发现，收入-rs12666409-rs129915-rs1611114交互对于海洛因依赖后的记忆变化产生了最高的测试平衡准确性和交叉验证一致性。我们的结果表明，海洛因依赖后的记忆变化是遗传和环境相结合的结果。这一发现可能导致对海洛因依赖性的更好理解，并进一步改善个性化治疗。我们的结果表明，海洛因依赖后的记忆变化是遗传和环境相结合的结果。这一发现可能导致对海洛因依赖性的更好理解，并进一步改善个性化治疗。我们的结果表明，海洛因依赖后的记忆变化是遗传和环境相结合的结果。这一发现可能导致对海洛因依赖性的更好理解，并进一步改善个性化治疗。