Association of the PLCB1 gene with drug dependence.
Association of the PLCB1 gene with drug dependence.
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DOI：
10.1038/s41598-017-10207-2
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发表时间：
2017-08-31
影响因子：
4.6
通讯作者：
Cormand B
中科院分区：
文献类型：
--
作者：
Cabana-Domínguez J;Roncero C;Pineda-Cirera L;Palma-Álvarez RF;Ros-Cucurull E;Grau-López L;Esojo A;Casas M;Arenas C;Ramos-Quiroga JA;Ribasés M;Fernàndez-Castillo N;Cormand B
与药物成瘾易感性有关的遗传因素在很大程度上仍然未知。miRNAs似乎在药物诱导的大脑可塑性中起着关键作用，这可能会导致成瘾的出现。在这项工作中，我们探索了miRNAs在药物成瘾中的作用。为此，我们选择了位于靶基因3 'UTR的62个SNP，这些SNP被预测会改变miRNA分子的结合，并在西班牙735例病例（主要是可卡因依赖受试者，具有多种药物依赖性）和739例对照中进行了病例-对照关联研究。我们发现PLCB 1基因中的rs 1047383与药物依赖之间存在关联，该关联在独立样本（663例病例和667例对照）中得到了复制。然后，我们选择了9个预测与rs 1047383区域结合的miRNAs，但没有一个对PLCB 1表达有任何影响。我们还评估了两种miRNAs结合区域，该区域含有与rs 1047383连锁不平衡的SNP，但尽管发现其中一种hsa-miR-582下调PLCB 1，但等位基因之间没有观察到差异。最后，我们探讨了可卡因改变PLCB 1表达的可能性，我们观察到可卡因滥用者的脑桥核和可卡因治疗后的人多巴胺能样神经元中的基因显著上调。我们的研究结果，加上以前的研究，表明PLCB 1参与药物依赖的易感性。
Genetic factors involved in the susceptibility to drug addiction still remain largely unknown. MiRNAs seem to play key roles in the drug-induced plasticity of the brain that likely drives the emergence of addiction. In this work we explored the role of miRNAs in drug addiction. With this aim, we selected 62 SNPs located in the 3’UTR of target genes that are predicted to alter the binding of miRNA molecules and performed a case-control association study in a Spanish sample of 735 cases (mainly cocaine-dependent subjects with multiple drug dependencies) and 739 controls. We found an association between rs1047383 in the PLCB1 gene and drug dependence that was replicated in an independent sample (663 cases and 667 controls). Then we selected 9 miRNAs predicted to bind the rs1047383 region, but none of them showed any effect on PLCB1 expression. We also assessed two miRNAs binding a region that contains a SNP in linkage disequilibrium with rs1047383, but although one of them, hsa-miR-582, was found to downregulate PLCB1, no differences were observed between alleles. Finally, we explored the possibility that PLCB1 expression is altered by cocaine and we observed a significant upregulation of the gene in the nucleus accumbens of cocaine abusers and in human dopaminergic-like neurons after cocaine treatment. Our results, together with previous studies, suggest that PLCB1 participates in the susceptibility to drug dependence.
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影响因子：
25
作者：
Im, Heh-In;Hollander, Jonathan A.;Bali, Purva;Kenny, Paul J.
通讯作者：
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