背景:遗传变异可能影响美沙酮代谢,剂量要求,和复发的风险。
目的:为了确定CYP2B6*6或ABCB1(rs1045642)多态性是否与美沙酮反应(血浆浓度,剂量,或对治疗的反应)。
方法:两名独立审稿人搜索Medline,EMBASE,CINAHL,PsycINFO,和WebofScience数据库。我们纳入了报道美沙酮血浆浓度的研究,美沙酮反应,或美沙酮剂量与CYP2B6*6或ABCB1多态性有关。
结果:我们筛选了182篇文章,提取了7篇文章纳入荟萃分析。在标题上的两个独立评分者之间观察到了相当大的协议(kappa,0.82),abstract(kappa,0.43),和全文筛选(kappa,0.43)。与非携带者相比,CYP2B6*6纯合携带者的Trough(R)美沙酮血浆浓度明显更高(标准化平均差[SMD]=0.53,95%置信区间[CI],0.05-1.00,p=0.03),异质性最小(I(2)=0%)。同样,与非携带者相比,*6单倍型纯合携带者的谷(S)美沙酮血浆浓度更高,(SMD=1.44,95%CI0.27-2.61,p=0.02)然而观察到显著的异质性(I(2)=69%)。未发现CYP2B6*6单倍型的携带者在剂量或对治疗的反应方面与非携带者显著不同。我们发现ABCB1多态性与波谷(R)之间没有显着关联,(S)血浆浓度,美沙酮剂量,或美沙酮反应。
结论:尽管纳入的研究数量和样本量不大,这是第一个荟萃分析,显示CYP2B6*6基因型纯合的参与者有较高的谷(R)和(S)美沙酮血浆浓度,表明*6个纯合携带者的美沙酮代谢明显较慢。
BACKGROUND: Genetic variability may influence methadone metabolism, dose requirements, and risk of relapse.
OBJECTIVE: To determine whether the CYP2B6*6 or ABCB1 (rs1045642) polymorphisms are associated with variation in methadone response (plasma concentration, dose, or response to treatment).
METHODS: Two independent reviewers searched Medline, EMBASE, CINAHL, PsycINFO, and Web of Science databases. We included studies that reported methadone plasma concentration, methadone response, or methadone dose in relation to the CYP2B6*6 or ABCB1 polymorphisms.
RESULTS: We screened 182 articles and extracted 7 articles for inclusion in the meta-analysis. Considerable agreement was observed between the two independent raters on the title (kappa, 0.82), abstract (kappa, 0.43), and full text screening (kappa, 0.43). Trough (R) methadone plasma concentration was significantly higher in CYP2B6*6 homozygous carriers when compared to non-carriers (standardized mean difference [SMD] = 0.53, 95% confidence interval [CI], 0.05-1.00, p = 0.03) with minimal heterogeneity (I(2) = 0%). Similarly, trough (S) methadone plasma concentration was higher in homozygous carriers of the *6 haplotype when compared to non-carriers, (SMD = 1.44, 95% CI 0.27-2.61, p = 0.02) however significant heterogeneity was observed (I(2) = 69%). Carriers of the CYP2B6*6 haplotype were not found to be significantly different from non-carriers with respect to dose or response to treatment. We found no significant association between the ABCB1 polymorphism and the trough (R), (S) plasma concentrations, methadone dose, or methadone response.
CONCLUSIONS: Although the number of studies included and sample size were modest, this is the first meta analysis to show participants homozygous for the CYP2B6*6 genotype have higher trough (R) and (S) methadone plasma concentrations, suggesting that methadone metabolism is significantly slower in *6 homozygous carriers.