CYP2B6 SNPs are associated with methadone dose required for effective treatment of opioid addiction.
CYP2B6 SNPs are associated with methadone dose required for effective treatment of opioid addiction.
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DOI：
10.1111/j.1369-1600.2011.00349.x
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发表时间：
2013-07
影响因子：
3.4
通讯作者：
Kreek MJ
中科院分区：
文献类型：
--
作者：
Levran O;Peles E;Hamon S;Randesi M;Adelson M;Kreek MJ
在阿片成瘾的美沙酮维持治疗(MMT)中，适当的美沙酮剂量是治疗成功的关键。剂量测定的挑战之一是剂量反应的个体间变异性。美沙酮代谢主要归因于细胞色素P450酶细胞色素3A4、细胞色素P2B6和细胞色素P2D6。[SNPs 785A&Gt；G(Rs2279343)和516G&Gt；T(Rs3745274)]与美沙酮代谢缓慢相关。为探讨CYP2B6*6等位基因对美沙酮剂量需求的影响，对74例以色列海洛因依赖者进行了基因分型。根据血统信息标记(AIMS)，样本主要是中东/欧洲血统。只包括没有可能影响美沙酮代谢的主要联合用药的患者。该样本美沙酮的稳定日剂量范围为13-260毫克(平均140±52毫克)。CYP2B6基因785A>；G和516G>；T变异等位基因纯合子受试者所需美沙酮平均剂量(分别为88、96 mg)显著低于杂合子受试者(分别为133、129 mg)和非携带者(分别为150、151 mg)(名义P分别为0.012、0.048)。在控制了年龄、性别和ABCB1SNP 1236C>；T(Rs1128503)后，结果仍然有意义，这些SNP以前被证明与该人群的高美沙酮剂量需求有关(分别为P=0.006和0.030)。对另外77个CYP2B6、CYP3A4和CYP2D6 SNPs进行了基因分型。其中，24个SNP是多态的，没有一个与美沙酮剂量有显著关联。为了在其他受试者和其他人群中重复这些初步发现，有必要进行进一步的研究。
Adequate methadone dosing in methadone maintenance treatment (MMT) for opioid addiction is critical for therapeutic success. One of the challenges in dose determination is the inter-individual variability in dose response. Methadone metabolism is attributed primarily to cytochrome P450 enzymes CYP3A4, CYP2B6, and CYP2D6. The CYP2B6*6 allele [SNPs 785A>G (rs2279343) and 516G>T (rs3745274)] was associated with slow methadone metabolism. To explore the effects of CYP2B6*6 allele on methadone dose requirement, it was genotyped in a well-characterized sample of 74 Israeli former heroin addicts in MMT. The sample is primarily of Middle Eastern/European ancestry, based on ancestry informative markers (AIMs). Only patients with no major co-medication that may affect methadone metabolism were included. The stabilizing daily methadone dose in this sample ranges between 13-260 mg (mean 140±52 mg). The mean methadone doses required by subjects homozygous for the variant alleles of the CYP2B6 SNPs 785A>G and 516G>T (88, 96 mg, respectively) were significantly lower than those of the heterozygotes (133, 129 mg, respectively) and the non-carriers (150, 151 mg, respectively) (nominal P = 0.012, 0.048, respectively). The results remain significant after controlling for age, sex and the ABCB1 SNP 1236C>T (rs1128503), that was previously shown to be associated with high methadone dose requirement in this population (P = 0.006, 0.030, respectively). An additional 77 CYP2B6, CYP3A4 and CYP2D6 SNPs were genotyped. Of these, 24 SNPs were polymorphic and none showed significant association with methadone dose. Further studies are necessary to replicate these preliminary findings in additional subjects and other populations.
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影响因子：
6.7
作者：
通讯作者：
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影响因子：
3.5
作者：
Levran, Orna;O'Hara, Kimberly;Kreek, Mary Jeanne
通讯作者：
Kreek, Mary Jeanne
影响因子：
6.7
作者：
Eap, C. B.;Crettol, S.;Abriel, H.
通讯作者：
Abriel, H.
影响因子：
6.7
作者：
Bunten, H.;Liang, W. J.;Osselton, D.
通讯作者：
Osselton, D.
DOI：
10.2165/00129785-200404060-00006
发表时间：
2004-01-01
期刊：
American journal of pharmacogenomics : genomics-related research in drug development and clinical practice
影响因子：
--
作者：
Luo, Huai-Rong;Aloumanis, Vasileios;Wan, Yu-Jui Yvonne
通讯作者：
Wan, Yu-Jui Yvonne