Opioid and Dopamine Genes Interact to Predict Naltrexone Response in a Randomized Alcohol Use Disorder Clinical Trial.
Opioid and Dopamine Genes Interact to Predict Naltrexone Response in a Randomized Alcohol Use Disorder Clinical Trial.
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DOI：
10.1111/acer.14431
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发表时间：
2020-10
期刊：
影响因子：
--
通讯作者：
Schacht JP
中科院分区：
文献类型：
--
作者：
Anton RF;Voronin KE;Book SW;Latham PK;Randall PK;Glen WB;Hoffman M;Schacht JP
虽然阿片拮抗剂纳洛酮被批准用于酒精使用障碍（AUD），但并不是每个人都受益。这项研究评估了OPRM 1 SNP rs 1799971是否与多巴胺转运蛋白基因DAT 1/SLC 6A 3 VNTR rs 28363170或儿茶酚-O-甲基转移酶（COMT）基因SNP rs 4680相互作用，以预测纳洛酮反应。符合DSM-IV酒精依赖的个体根据他们的OPRM 1基因型（75个G等位基因携带者和77个A等位基因纯合子）以及DAT 1 VNTR（9对10个重复）或COMT SNP（瓦尔/瓦尔对met携带者）的基因分型被随机分配到纳洛酮（50 mg/天）或安慰剂组。在16周内和治疗结束时评价重度饮酒天数（%HDD）。根据基因型计算纳洛酮反应的效应量（d）。与安慰剂相比，纳洛酮显著降低了同时患有DAT 1 10/10的OPRM 1 G携带者的%HDD（p=0.021，d=0.72）或COMT瓦尔/瓦尔基因型（p=0.05，d=0.80），并且在那些同时也是DAT 19-重复携带者的OPRM 1A纯合子中程度较低（p=0.09，d=0.70）或COMT符合携带者（p=0.03，d=0.63）。所有其他基因型组合对纳洛酮无差异反应。腹泻/腹痛在OPRM 1A纯合子中更突出，这些纯合子也是DAT 9或COMT met携带者。这些结果表明，具有阿片类药物敏感基因型的AUD个体（OPRM 1 G携带者）如果具有表明多巴胺水平正常/较低的基因型，则对纳洛酮的反应更好（DAT 1 10、10或COMT瓦尔、瓦尔），而那些对阿片类药物反应较低的基因型（OPRM 1A纯合子）如果具有指示更大多巴胺张力的基因型（DAT 19-重复或COMT met携带者），则对纳洛酮响应更好。这些结果可能会导致更个性化的AUD治疗。
While the opiate antagonist, naltrexone, is approved for Alcohol Use Disorder (AUD), not everyone benefits. This study evaluated whether the OPRM1 SNP rs1799971 interacts with the dopamine transporter gene DAT1/SLC6A3 VNTR rs28363170 or the catechol-o-methyltransferase (COMT) gene SNP rs4680 in predicting naltrexone response. Individuals who met DSM-IV alcohol dependence were randomly assigned to naltrexone (50 mg/day) or placebo based on their OPRM1 genotype (75 G allele carriers and 77 A allele homozygotes) and also genotyped for DAT1 VNTR (9 vs 10 repeats) or COMT SNP (val/val vs. met carriers). Heavy drinking days (%HDD) were evaluated over 16 weeks and at the end of treatment. Effect sizes (d) for naltrexone response were calculated based on genotypes. Naltrexone, relative to placebo, significantly reduced %HDD among OPRM1 G carriers who also had DAT1 10/10 (p=0.021, d=0.72) or COMT val/val genotypes (p=0.05, d=0.80), and to a lesser degree in those OPRM1 A homozygotes who were also DAT1 9-repeat carriers (p=0.09, d=0.70) or COMT met carriers (p=0.03, d=0.63). All other genotype combinations showed no differential response to naltrexone. Diarrhea/abdominal pain was more prominent in OPRM1 A homozygotes who were also DAT 9 or COMT met carriers. These results suggest that Individuals with AUD with a more opioid-responsive genotype (OPRM1 G carriers) respond better to naltrexone if they have genotypes indicating normal/less dopamine tone (DAT1 10,10 or COMT val,val), while those with a less responsive opioid-responsive genotype (OPRM1 A homozygotes) respond better to naltrexone if they have genotypes indicating greater dopamine tone (DAT1 9-repeat or COMT met carriers). These results could lead to more personalized AUD treatments.
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影响因子：
3.4
作者：
Greenfield, Thomas K.;Ye, Yu;Kranzler, Henry R.
通讯作者：
Kranzler, Henry R.
影响因子：
2.7
作者：
Benjamini, Yoav;Krieger, Abba M.;Yekutieli, Daniel
通讯作者：
Yekutieli, Daniel
DOI：
10.1111/j.1530-0277.2006.00225.x
发表时间：
2006-11-01
影响因子：
3.2
作者：
Anton, Raymond F.;Youngblood, Marston
通讯作者：
Youngblood, Marston
影响因子：
4.4
作者：
Forcehimes, Alyssa A.;Tonigan, J. Scott;Baer, John S.
通讯作者：
Baer, John S.
DOI：
10.15288/jsas.2005.s15.56
发表时间：
2005-07-01
期刊：
JOURNAL OF STUDIES ON ALCOHOL
影响因子：
--
作者：
Goldman, D;Oroszi, G;Anton, R
通讯作者：
Anton, R