GAD1 but not GAD2 polymorphisms are associated with heroin addiction phenotypes
GAD1 but not GAD2 polymorphisms are associated with heroin addiction phenotypes
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DOI：
10.1016/j.neulet.2019.134704
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发表时间：
2019-12
影响因子：
2.5
通讯作者：
Yuhui Shi;Yunxiao Li;Jinyu Zhang;Yifan Xiao;Peng Yan;Yongsheng Zhu
中科院分区：
文献类型：
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作者：
Yuhui Shi;Yunxiao Li;Jinyu Zhang;Yifan Xiao;Peng Yan;Yongsheng Zhu
海洛因成瘾是一种慢性复杂的脑部疾病，包含多种表型，在成瘾者之间差异很大，可能受遗传因素的影响。本研究共招募了801名无亲缘关系的海洛因依赖者，并根据海洛因依赖的8种表型将其分为不同的亚组。采用SNaPshot法对inGAD1多态性（rs3762555、rs3762556、rs3791878、rs3749034、rs11532313和rs769395）和gad2多态性（rs2839669、rs2839670和rs2236418）进行基因分型。遗传变异与8种表型之间的关系主要通过二元逻辑回归进行评估。结果gad1rs3749034和rs3762555等位基因的频率与海洛因成瘾后的日美沙酮用量和记忆变化有关。gad1rs3762556的C等位基因频率与较低的日美沙酮使用剂量相关。InGAD1、rs3762556、rs3762555、rs3791878和rs3749034 snp具有较强的连锁，且C-G-C-A单倍型出现频率在美沙酮低剂量组较高。TT基因型rs11542313患者的美沙酮维持剂量低于CC基因型患者。在记忆减少组，rs3762555和rs3749034的G等位基因较低，而rs11542313的T等位基因较高。gad2与海洛因成瘾表型的关联分析结果无显著差异。结论ad1基因多态性与汉人群海洛因依赖表型，尤其是美沙酮日用量和记忆变化有关。这些结果可能为海洛因成瘾的治疗提供个体化指导。
IntroductionHeroin addiction is a chronic complex brain disease that contains multiple phenotypes, which vary widely among addicts and may be affected by genetic factors. A total of 801 unrelated heroin addicts were recruited and divided into different subgroups according to eight phenotypes of heroin addiction. Polymorphisms inGAD1(rs3762555, rs3762556, rs3791878, rs3749034, rs11532313 and rs769395) andGAD2(rs2839669, rs2839670 and rs2236418) were genotyped using the SNaPshot assay. Associations between genetic variants and the eight phenotypes were mainly assessed by binary logistic regression.ResultsWe found that the frequencies of G allele ofGAD1rs3749034 and rs3762555 were associated with daily dose of methadone use and memory change after heroin addiction. The C allele frequency ofGAD1rs3762556 was associated with lower daily dose of methadone use. InGAD1, SNPs rs3762556, rs3762555, rs3791878 and rs3749034 had strong linkage, and the frequency of the C-G-C-A haplotype was higher in the lower dose of methadone group. Patients with the TT genotype of rs11542313 were maintained on lower dose of methadone than patients with the CC genotype. The G alleles of rs3762555 and rs3749034 were lower, while the T allele of rs11542313 was higher, in the memory decreased group. The results of association analyses ofGAD2with phenotypes of heroin addiction showed no significant differences.ConclusionGAD1polymorphisms were associated with phenotypes of heroin addiction, especially the daily dose of methadone use and memory change in the Han Chinese population. These results may provide individualized guidance for the treatment of heroin addiction.