The Vulnerability to Methamphetamine Dependence and Genetics: A Case-Control Study Focusing on Genetic Polymorphisms at Chromosomal Region 5q31.3.
The Vulnerability to Methamphetamine Dependence and Genetics: A Case-Control Study Focusing on Genetic Polymorphisms at Chromosomal Region 5q31.3.
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甲基苯丙胺依赖和遗传学的脆弱性：关注染色体区域 5q31.3 遗传多态性的病例对照研究
DOI：
10.3389/fpsyt.2022.870322
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发表时间：
2022
影响因子：
4.7
通讯作者：
Guan, Fanglin
中科院分区：
文献类型：
--
作者：
Xiao, Jing;Ma, Yitian;Wang, Xiaochen;Wang, Changqing;Li, Miao;Liu, Haobiao;Han, Wei;Wang, Huiying;Zhang, Wenpei;Wei, Hang;Zhao, Longrui;Zhang, Tianxiao;Lin, Huali;Guan, Fanglin
甲基苯丙胺（METH）是一种中枢神经兴奋剂，也是最常被使用的非法药物之一。许多影响复杂性状（包括酗酒）的基因位点已被发现；然而，对甲基苯丙胺依赖的基因分析仍然有限。在甲基苯丙胺自我给药戒断后，在背内侧纹状体的Fos阳性神经元中检测到组蛋白去乙酰化酶3（HDAC3）表达增加。在此，我们旨在系统地研究HDAC3对中国汉族人群甲基苯丙胺依赖易感性的影响。
我们总共招募了1221名甲基苯丙胺依赖患者以及2328名年龄和性别匹配的对照。对于基因分型，我们选择了位于HDAC3±3kb区域内的14个单核苷酸多态性（SNPs）。使用PLINK通过基于单个标记和单倍型的方法检测基因分型的基因多态性与甲基苯丙胺依赖易感性之间的关联。使用基因型 - 组织表达（GTEx）数据库研究表达数量性状位点（eQTLs）对靶基因表达的影响。
SNP rs14251被确定为一个显著的关联信号（χ² = 9.84，P = 0.0017）。甲基苯丙胺依赖风险增加与rs14251的A等位基因（次要等位基因）相关[比值比（95%置信区间）= 1.25（1.09 - 1.43）]。计算机模拟分析结果表明，SNP rs14251在各种人体组织中可能是FCHSD1、PCDHGB6和RELL2的潜在eQTL信号，但不是HDAC3的。
我们证明了位于5q31.3的基因多态性rs14251与中国汉族人群甲基苯丙胺依赖易感性显著相关。
Methamphetamine (METH) is a central nervous psychostimulant and one of the most frequently used illicit drugs. Numerous genetic loci that influence complex traits, including alcohol abuse, have been discovered; however, genetic analyses for METH dependence remain limited. An increased histone deacetylase 3 (HDAC3) expression has been detected in Fos-positive neurons in the dorsomedial striatum following withdrawal after METH self-administration. Herein, we aimed to systematically investigate the contribution of HDAC3 to the vulnerability to METH dependence in a Han Chinese population. In total, we recruited 1,221 patients with METH dependence and 2,328 age- and gender-matched controls. For genotyping, we selected 14 single nucleotide polymorphisms (SNPs) located within ± 3 kb regions of HDAC3. The associations between genotyped genetic polymorphisms and the vulnerability to METH dependence were examined by single marker- and haplotype-based methods using PLINK. The effects of expression quantitative trait loci (eQTLs) on targeted gene expressions were investigated using the Genotype-Tissue Expression (GTEx) database. The SNP rs14251 was identified as a significant association signal (χ2 = 9.84, P = 0.0017). An increased risk of METH dependence was associated with the A allele (minor allele) of rs14251 [odds ratio (95% CI) = 1.25 (1.09–1.43)]. The results of in silico analyses suggested that SNP rs14251 could be a potential eQTL signal for FCHSD1, PCDHGB6, and RELL2, but not for HDAC3, in various human tissues. We demonstrated that genetic polymorphism rs14251 located at 5q31.3 was significantly associated with the vulnerability to METH dependence in Han Chinese population.
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