College of Forensic Science, Xi'an Jiaotong University, Shaanxi 710061, China.
Department of Anatomy, Shanxi University of Chinese Medicine, Shaanxi 712046, China.
Neurosci Lett. 2021 Mar 23;748:135677. doi: 10.1016/j.neulet.2021.135677. Epub 2021 Feb 9.
Heroin use disorder is a chronic relapsing brain disease containing multiple phenotypes. These phenotypes vary among heroin users and might be influenced by genetic factors. Single-nucleotide polymorphisms (SNPs) of catechol-O-methyltransferase (COMT) and alpha-1-adrenergic receptor (ADRA1A) genes are associated with heroin use disorder. However, it has not been clarified which phenotypes of heroin use disorder are related to these genes. To address this question, we recruited 801 unrelated heroin users and divided them into different subgroups according to four important phenotypes of heroin use disorder. Then 7 SNPs in the functional region of these genes were systematically screened and genotyped using a SNaPshot assay. We found that the A allele of ADRA1A rs1048101 was associated with a shorter duration of transition from first use to addiction. Subjects with the C allele of ADRA1A rs3808585 were more susceptible to memory impairment after heroin use disorder. Subjects with the G allele of COMT rs769224 were more likely to take a higher dose of heroin every day. Our study confirmed the association between polymorphisms of COMT and ADRA1A with those specific phenotypes of heroin use disorder, which will be instructive for the precise treatment of the disease.
海洛因使用障碍是一种慢性复发性脑部疾病，包含多种表型。这些表型在海洛因使用者中存在差异，可能受到遗传因素的影响。儿茶酚-O-甲基转移酶（COMT）和α-1-肾上腺素能受体（ADRA1A）基因的单核苷酸多态性（SNPs）与海洛因使用障碍有关。然而，目前尚不清楚这些基因与海洛因使用障碍的哪些表型有关。为了解决这个问题，我们招募了 801 名无血缘关系的海洛因使用者，并根据海洛因使用障碍的四个重要表型将他们分为不同的亚组。然后，我们使用 SNaPshot 测定法系统筛选和基因分型了这些基因功能区域的 7 个 SNP。我们发现 ADRA1A rs1048101 的 A 等位基因与首次使用到成瘾之间的时间缩短有关。ADRA1A rs3808585 的 C 等位基因携带者在海洛因使用障碍后更容易出现记忆障碍。COMT rs769224 的 G 等位基因携带者每天更有可能服用更高剂量的海洛因。我们的研究证实了 COMT 和 ADRA1A 基因多态性与海洛因使用障碍特定表型之间的关联，这将有助于对该疾病进行精确治疗。
