Pharmacogenetics of naltrexone and disulfiram in alcohol dependent, dually diagnosed veterans.
Pharmacogenetics of naltrexone and disulfiram in alcohol dependent, dually diagnosed veterans.
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DOI：
10.1111/j.1521-0391.2014.12102.x
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发表时间：
2014-05
期刊：
影响因子：
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通讯作者：
Petrakis IL
中科院分区：
文献类型：
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作者：
Arias AJ;Gelernter J;Gueorguieva R;Ralevski E;Petrakis IL
我们从一项治疗酒精依赖的药物治疗研究中探索了与情绪、焦虑和精神障碍共存的受试者的药物遗传学相互作用。酒精依赖(AD)受试者接受纳曲酮单独治疗、单纯安慰剂治疗、双硫仑加安慰剂治疗或双硫仑加纳曲酮治疗。对它们进行了OPRM1 rs1799971(Asn40Asp)和DBH rs1611115(C-1021T)的基因分型。N=107名欧洲裔美国男性受试者。与OPRM1没有显著的相互作用。DBH和纳曲酮对戒酒的主要结局有交互作用(Χ2(1)=5.2 3，p=0.0 2)。与服用纳曲酮的“CC”受试者相比，服用纳曲酮的“T”等位基因携带者有更多的禁欲。服用纳曲酮的“T”等位基因携带者戒酒率最高(>；90%)。此外，在每天饮酒时，胸径基因与二硫氰胺有交互作用(p=0.01)，在二硫胺试验中，CC基因携带者的饮酒量比T等位基因携带者少。Dbh*rs1611115*T与纳曲酮的反应更好有关，而对于那些服用双硫仑饮酒的人来说，“CC”受试者比T携带者喝得更少。Rs1611115基因分型可能有助于了解AD治疗反应的个体间差异。有必要对rs1611115进行进一步的药物遗传学研究。
We explored pharmacogenetic interactions in subjects from a medication treatment study for alcohol dependence in subjects with co-occurring mood, anxiety, and psychotic disorders. Alcohol dependent (AD) subjects received naltrexone alone, placebo alone, disulfiram with placebo or disulfiram with naltrexone. They were genotyped for OPRM1 rs1799971 (Asn40Asp), and DBH rs1611115 (C-1021T). N=107 male European-American subjects were included. There were no significant interactions with OPRM1. DBH interacted with naltrexone on the primary outcome of abstinence from heavy drinking, (Χ2(1)=5.23, p=0.02). “T” allele carriers on naltrexone had more abstinence compared to “CC” subjects on naltrexone. “T” allele carriers on naltrexone had the highest overall rates of abstinence from heavy drinking (>90%). Also, DBH genotype interacted with disulfram (p=0.01) on drinks per drinking day with less drinking for subjects with the “CC” genotype than for T allele carriers on disulfiram. DBH*rs1611115*T associated with better response to naltrexone, while for those on disulfiram that drank, “CC” subjects drank less than T carriers. Genotyping rs1611115 may be useful in understanding inter-individual differences in AD treatment response. Further study of rs1611115 pharmacogenetics is warranted.