RELATIONSHIP BETWEEN ABCB1 POLYMORPHISMS AND METHADONE DOSAGE REQUIREMENTS IN OPIOID-DEPENDENT PATIENTS

Trần Văn Chiều1,, Trần Khánh Chi1, Nguyễn Quỳnh Giao1, Lê Hoàng Nam2, Đặng Thị Ngọc Dung1
1 Hanoi Medical University
2 Center for Disease Control in Ninh Binh province

Main Article Content

Abstract

Methadone is an opioid pain reliever used to treat patients with opioid addiction. However, It is difficult to determine the dose of methadone because of the large variability in response to treatment among individuals. Methadone is transported into cells through the P-glycoprotein (P-pg) protein, which is encoded by the ABCB1 (MRD1) gene. In many studies show that this gene was a highly polymorphic with many genetic variations. These genetic variants were important role in the expression of P-glycoprotein so as affected to methadone metabolism. Objective: This study was performed to identify single nucleotide polymorphisms 1236C>T (dbSNP rs1128503), 2677G>T/A (dbSNP rs2032582), and 3435C>T (dbSNP rs1045642) of the ABCB1 gene in patients with substance abuse opiates for methadone replacement therapy and to assess the relationship with baseline dose. Material and methods: 400 opiate-addicted patients receiving methadone treatment were identified for single nucleotide polymorphisms by Sanger gene sequencing. Results: The individuals carrying the T variant of the single nucleotide polymorphism 3435C>T (dbSNP rs1045642) has methadon dose higher 1,556 times more than individuals without this variant (dbSNP rs1045642) in group which received methadone dose ≥ 90 mg/day (OR: 1,556, p=0.032). Conclusion: There is an association between the ABCB1 gene variant and the dose of methadone replacement therapy. Genotyping of the ABCB1 gene in opiate-addicted patients receiving methadone replacement therapy may help individualize treatment.

Article Details

References

1. Hodges LM, Markova SM, Chinn LW, et al. Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenet Genomics. 2011;21(3):152-161. doi:10.1097/FPC.0b013e3283385a1c
2. Csajka C, Crettol S, Guidi M, Eap CB. Population Genetic-Based Pharmacokinetic Modeling of Methadone and its Relationship with the QTc Interval in Opioid-Dependent Patients. Clin Pharmacokinet. 2016;55(12):1521-1533. doi:10.1007/s40262-016-0415-2
3. Hoffmeyer S, Burk O, von Richter O, et al. Functional polymorphisms of the human multidrug-resistance gene: Multiple sequence variations and correlation of one allele with P-glycoprotein expression and activity in vivo. Proc Natl Acad Sci U S A. 2000;97(7):3473-3478.
4. Teoh Bing Fei J, Yee A, Habil MHB, Danaee M. Effectiveness of Methadone Maintenance Therapy and Improvement in Quality of Life Following a Decade of Implementation. J Subst Abuse Treat. 2016;69:50-56. doi:10.1016/j.jsat.2016.07.006
5. Luo R, Li X, Qin S, et al. Impact of SNP–SNP interaction among ABCB1 , ARRB2 , DRD1 and OPRD1 on methadone dosage requirement in Han Chinese patients. Pharmacogenomics. 2017;18 (18):1659-1670. doi:10.2217/pgs-2017-0072
6. Levran O, O’Hara K, Peles E, et al. ABCB1 (MDR1) genetic variants are associated with methadone doses required for effective treatment of heroin dependence. Hum Mol Genet. 2008;17(14):2219-2227. doi:10.1093/hmg/ddn122
7. Hung CC, Chiou MH, Huang BH, et al. Impact of genetic polymorphisms in ABCB1, CYP2B6, OPRM1, ANKK1 and DRD2 genes on methadone therapy in Han Chinese patients. Pharmacogenomics. 2011;12(11):1525-1533. doi:10.2217/pgs.11.96
8. Bart G, Lenz S, Straka RJ, Brundage RC. Ethnic and genetic factors in methadone pharmacokinetics: A population pharmacokinetic study. Drug Alcohol Depend. 2014;145:185-193. doi:10.1016/j.drugalcdep.2014.10.014