Pharmacogenetically driven treatments for alcoholism: are we there yet?
Pharmacogenetically driven treatments for alcoholism: are we there yet?
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DOI：
10.2165/11633180-000000000-00000
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发表时间：
2012-06-01
期刊：
影响因子：
6
通讯作者：
Sewell RA
中科院分区：
文献类型：
--
作者：
Arias AJ;Sewell RA
酒精依赖治疗的药理学分析试图预测特定药物的治疗反应和副作用风险。我们回顾了与酒精依赖治疗相关的药物遗传学文献，并描述了该领域药物遗传学研究的最新方法。两种主要的药物遗传学研究设计占主导地位：挑战研究和治疗试验分析。研究的药物包括美国fda批准的纳曲酮和阿坎普罗酸，这两种药物都用于治疗酒精依赖，以及一些研究（和标签外）治疗药物，如舍曲林、奥氮平和昂丹西琼。研究最充分的与酒精中毒治疗相关的功能性遗传变异是rs1799971，这是编码μ-阿片受体的OPRM1基因外显子1上的单核苷酸多态性。来自临床试验的证据表明，rs1799971变异G等位基因的存在可能预示着对阿片受体拮抗剂（如纳曲酮）有更好的治疗反应。来自临床试验的证据也表明，几种药物在药效学上与编码多巴胺能和血清素能神经传递的蛋白质的基因变异相互作用。编码多巴胺D4受体的DRD4基因的变异可能预示着对纳曲酮和奥氮平的更好反应。血清素转运基因SLC6A4启动子区域的多态性似乎与受试者对舍曲林的不同治疗反应有关，这取决于受试者开始酗酒的年龄。SLC6A4的遗传变异也可能与对昂丹司琼更好的治疗反应有关。在酒精研究中，最初的药物遗传学努力已经确定了具有潜在临床应用价值的功能变异，但需要更多的研究来进一步阐明这些药物遗传学相互作用的机制及其调节因子，以便将其转化为临床实践。
Pharmacogenetic analyses of treatments for alcohol dependence attempt to predict treatment response and side-effect risk for specific medications. We review the literature on pharmacogenetics relevant to alcohol dependence treatment, and describe state-of-the-art methods of pharmacogenetic research in this area. Two main pharmacogenetic study designs predominate: challenge studies and treatment-trial analyses. Medications studied include US FDA-approved naltrexone and acamprosate, both indicated for treating alcohol dependence, as well as several investigational (and off-label) treatments such as sertraline, olanzapine and ondansetron. The best-studied functional genetic variant relevant to alcoholism treatment is rs1799971, a single-nucleotide polymorphism in exon 1 of the OPRM1 gene that encodes the μ-opioid receptor. Evidence from clinical trials suggests that the presence of the variant G allele of rs1799971 may predict better treatment response to opioid receptor antagonists such as naltrexone. Evidence from clinical trials also suggests that several medications interact pharmacogenetically with variation in genes that encode proteins involved in dopaminergic and serotonergic neurotransmission. Variation in the DRD4 gene, which encodes the dopamine D4 receptor, may predict better response to naltrexone and olanzapine. A polymorphism in the serotonin transporter gene SLC6A4 promoter region appears related to differential treatment response to sertraline depending on the subject’s age of onset of alcoholism. Genetic variation in SLC6A4 may also be associated with better treatment response to ondansetron. Initial pharmacogenetic efforts in alcohol research have identified functional variants with potential clinical utility, but more research is needed to further elucidate the mechanism of these pharmacogenetic interactions and their moderators in order to translate them into clinical practice.
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影响因子：
9.8
作者：
Edenberg, HJ;Dick, DM;Begleiter, H
通讯作者：
Begleiter, H
影响因子：
4.2
作者：
Glatt, Stephen J.;Bousman, Chad;Tsuang, Ming T.
通讯作者：
Tsuang, Ming T.
影响因子：
2.6
作者：
Corvol, Harriet;De Giacomo, Anthony;Burchard, Esteban Gonzalez
通讯作者：
Burchard, Esteban Gonzalez
影响因子：
5.3
作者：
Gelernter, J;Kranzler, H;Cubells, JF
通讯作者：
Cubells, JF
DOI：
10.1002/ajmg.b.30091
发表时间：
2004-08-15
影响因子：
2.8
作者：
Covault, J;Gelernter, J;Kranzler, HR
通讯作者：
Kranzler, HR