Stolf Anderson R, Cupertino Renata B, Müller Diana, Sanvicente-Vieira Breno, Roman Tatiana, Vitola Eduardo S, Grevet Eugenio H, von Diemen Lisia, Kessler Felix H P, Grassi-Oliveira Rodrigo, Bau Claiton H D, Rovaris Diego L, Pechansky Flavio, Schuch Jaqueline B
Center for Drug and Alcohol Research, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
J Neural Transm (Vienna). 2019 Feb;126(2):193-199. doi: 10.1007/s00702-018-1946-5. Epub 2018 Oct 26.
There is evidence that dopamine receptors D2 (DRD2) and D4 (DRD4) polymorphisms may influence substance use disorders (SUD) susceptibility both individually and through their influence in the formation of DRD2-DRD4 heteromers. The dopaminergic role on the vulnerability to addiction appears to be influenced by sex. A cross-sectional study with 307 crack cocaine addicts and 770 controls was conducted. The influence of DRD2 rs2283265 and DRD4 48 bp VNTR in exon 3 variants, as well as their interaction on crack cocaine addiction susceptibility and severity were evaluated in women and men separately. An association between the DRD2 T allele and crack cocaine addiction was found in women. In this same group, interaction analysis demonstrated that the presence of DRD2-T allele and concomitant absence of DRD4-7R allele were associated with risk for crack cocaine addiction. No influence of DRD2 and DRD4 variants was observed in men regarding addiction severity. This study reinforces the role of dopaminergic genes in externalizing behaviors, especially the influence of DRD2-DRD4 interaction on SUD. This is the fourth sample that independently associated the DRD2-DRD4 interaction with SUD itself or related disorders. In addition, our findings point out to a potential difference of dopaminergic neurotransmission across sex influencing addiction susceptibility.
有证据表明，多巴胺受体D2（DRD2）和D4（DRD4）多态性可能单独影响物质使用障碍（SUD）易感性，也可能通过影响DRD2 - DRD4异聚体的形成来产生影响。多巴胺能在成瘾易感性方面的作用似乎受性别影响。开展了一项针对307名快克可卡因成瘾者和770名对照者的横断面研究。分别评估了DRD2 rs2283265和DRD4第3外显子48 bp可变数目串联重复序列（VNTR）变体的影响，以及它们对女性和男性快克可卡因成瘾易感性和严重程度的相互作用。在女性中发现DRD2 T等位基因与快克可卡因成瘾之间存在关联。在同一组中，相互作用分析表明，DRD2 - T等位基因的存在以及DRD4 - 7R等位基因的同时缺失与快克可卡因成瘾风险相关。在男性中未观察到DRD2和DRD4变体对成瘾严重程度有影响。本研究强化了多巴胺能基因在外部化行为中的作用，尤其是DRD2 - DRD4相互作用对SUD的影响。这是第四个将DRD2 - DRD4相互作用与SUD本身或相关疾病独立关联起来的样本。此外，我们的研究结果指出了跨性别多巴胺能神经传递在影响成瘾易感性方面的潜在差异。
