Genetic variation in OPRD1 and the response to treatment for opioid dependence with buprenorphine in European-American females.
Genetic variation in OPRD1 and the response to treatment for opioid dependence with buprenorphine in European-American females.
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DOI：
10.1038/tpj.2013.30
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发表时间：
2014-06
期刊：
影响因子：
--
通讯作者：
Berrettini WH
中科院分区：
文献类型：
--
作者：
Clarke TK;Crist RC;Ang A;Ambrose-Lanci LM;Lohoff FW;Saxon AJ;Ling W;Hillhouse MP;Bruce RD;Woody G;Berrettini WH
治疗阿片成瘾的两种常用处方药是美沙酮和丁丙诺啡。虽然这些药物在治疗阿片类药物依赖方面显示出一些效果，但治疗反应因个人而异。遗传因素很可能在决定治疗结果方面发挥作用。这项研究分析了编码增量阿片受体的基因OPRD1的6个多态性与582名阿片成瘾的欧洲美国人在24周的开放标签临床试验中随机服用美沙酮或丁丙诺啡/纳洛酮((Suboxone®))治疗结果的药物遗传学关联。治疗结果通过24周内遗漏或阿片类药物阳性尿液药物筛查的数量来评估。在总样本中，OPRD1中没有SNPs与两个治疗组的治疗结果显著相关。然而，性别分析发现了两个内含子SNPs(rs581111和rs529520)，它们预测了丁丙诺啡治疗女性的治疗结果。在接受丁丙诺啡治疗时，携带rs581111的AA或AG基因的女性患者的预后明显低于携带GG基因的患者(p=0.03，RR=1.67，95%C.I.[1.06-2.1])。在rs529520中，携带AA基因的女性的预后显著低于携带CC基因的女性(p=0.006，RR=2.15，95%C.I.[1.3-2.29])。在男性中没有发现明显的关联。这些发现表明，在考虑女性阿片成瘾者的治疗选择时，rs581111和rs52920可能是有用的，但需要在独立样本中进行确认。
Two commonly prescribed treatments for opioid addiction are methadone and buprenorphine. While these drugs show some efficacy in treating opioid dependence, treatment response varies among individuals. It is likely that genetic factors play a role in determining treatment outcome. This study analyses the pharmacogenetic association of 6 polymorphisms in OPRD1, the gene encoding the delta-opioid receptor, on treatment outcome in 582 opioid addicted European Americans randomized to either methadone or buprenorphine/naloxone ((Suboxone®) over the course of a 24 week open-label clinical trial. Treatment outcome was assessed as the number of missed or opioid positive urine drug screens over the 24 weeks. In the total sample, no SNPs in OPRD1 were significantly associated with treatment outcome in either treatment arm. However, sex-specific analyses revealed 2 intronic SNPs (rs581111 and rs529520) that predicted treatment outcome in females treated with buprenorphine. Females with the AA or AG genotypes at rs581111 had significantly worse outcomes than those with the GG genotype when treated with buprenorphine (p=0.03, RR=1.67, 95% C.I.[1.06-2.1]). For rs529520, females with the AA genotype had a significantly worse outcome than those with the CC genotype when (p=0.006, RR=2.15, 95%C.I.[1.3-2.29]). No significant associations were detected in males. These findings suggest that rs581111 and rs52920 may be useful when considering treatment options for female opioid addicts, however confirmation in an independent sample is warranted.
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DOI：
10.1073/pnas.1009923107
发表时间：
2010-11-16
影响因子：
11.1
作者：
Chakrabarti, Sumita;Liu, Nai-Jiang;Gintzler, Alan R.
通讯作者：
Gintzler, Alan R.
影响因子：
2.9
作者：
Ambrose-Lanci, Lisa M.;Peiris, Niluk B.;Van Bockstaele, Elisabeth J.
通讯作者：
Van Bockstaele, Elisabeth J.
影响因子：
105.7
作者：
FARRELL, M;WARD, J;STRANG, J
通讯作者：
STRANG, J
影响因子：
82.9
作者：
Gear, RW;Miaskowski, C;Levine, JD
通讯作者：
Levine, JD
影响因子：
2.7
作者：
ANGLIN, MD;HSER, YI;MCGLOTHLIN, WH
通讯作者：
MCGLOTHLIN, WH