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. 2013 May;14(7):755-68.
doi: 10.2217/pgs.13.58.

Association of genetic variation in pharmacodynamic factors with methadone dose required for effective treatment of opioid addiction

Orna Levran  1 , Einat Peles, Matthew Randesi, Xu Shu, Jurg Ott, Pei-Hong Shen, Miriam Adelson, Mary Jeanne Kreek
Affiliations

Association of genetic variation in pharmacodynamic factors with methadone dose required for effective treatment of opioid addiction

Orna Levran et al. Pharmacogenomics. 2013 May.

Abstract

Aim: The interindividual variability in the dose required for effective methadone maintenance treatment (MMT) for opioid addiction may be influenced in part by genetic variations in genes encoding pharmacodynamic factors of methadone. This study was conducted to identify some of these variants.

Materials & methods: This study focused on 11 genes encoding components of the opioidergic (OPRM1, POMC and ARRB2), the dopaminergic (ANKK1 and DRD2) and the glutamatergic pathways (GRIN1 and GRIN2A), as well as the neurotrophin system (NGFB, BDNF, NTRK1 and NTRK2). The study includes 227 Israeli patients undergoing stable MMT.

Results: Out of the 110 variants analyzed, 12 SNPs (in BDNF, NTRK2, OPRM1, DRD2 and ANKK1) were associated with methadone dose (nominal p < 0.05). Of these SNPs, ANKK1 rs7118900 and DRD2 rs2283265 are known to affect gene expression. Logistic regression of five representative SNPs discriminated between individuals requiring a methadone dose of >120 mg/day and <120 mg/day (p = 0.019), and showed moderate sensitivity and specificity (AUC of 0.63 in receiver operating characteristic analysis).

Conclusion: This data should stimulate further research on the potential influence and clinical significance of these variants on MMT.

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Figures

Figure 1
Figure 1. Distribution of the methadone doses
Arrow represents the mean.
Figure 2
Figure 2. Receiver operating characteristic curve showing the predictive power of the five selected SNPs (AUC = 0.63)
The diagonal line represents no predictive ability (AUC = 0.5). ROC: Receiver operating characteristic.
See this image and copyright information in PMC

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