@article{dafce39a1b044ea981f1141684cccab4,
title = "ABCB1 (MDR1) genetic variants are associated with methadone doses required for effective treatment of heroin dependence",
abstract = "Methadone is a mu-opioid receptor agonist used for treating opiate dependence. The range of effective methadone doses is broad. Part of the large inter-individual variability in efficacy may be accounted for by genetic factors. Methadone is a substrate of the transporter P-glycoprotein (P-gp) 170 that is encoded by the ABCB1 (MDR1) gene. Thus, P-gp variants may play a role in methadone absorption and distribution. We assessed the association between ABCB1 polymorphisms and methadone dose requirements in 98 methadone-maintained patients. The stabilizing methadone doses were normally distributed with a mean and median dose of 160 mg/day (range 30-280 mg/day). Statistical analysis showed significant difference in genotype frequencies between the 'higher' (>150 mg/day) and 'lower' (≤150 mg/day) methadone dose groups for single nucleotide polymorphism (SNP) 1236C>T (rs1128503) (experiment-wise P = 0.0325). Furthermore, individuals bearing the 3-locus genotype pattern TT-TT-TT (rs1045642, rs2032582 and rs1128503) have an approximately 5-fold chance of requiring the 'higher' methadone dose, while individuals heterozygous for these three SNPs have an approximately 3-fold chance of stabilizing at the 'lower' methadone dose (point-wise P-value = 0.026). These data suggest that specific ABCB1 variants may have clinical relevance by influencing the methadone dose required to prevent withdrawal symptoms and relapse in this population.",
author = "Orna Levran and Kimberly O'Hara and Einat Peles and Dawei Li and Sandra Barral and Brenda Ray and Lisa Borg and Jurg Ott and Miriam Adelson and Kreek, {Mary Jeanne}",
note = "Funding Information: National Institute of Health (DA-P60-05130 and DA-K05 -00049) to M.J.K., (MH-R01-44292) to J.O., National Natural Science Foundation of China (30730057) from the Chinese Government to J.O. and National Institute of Health/ NCRR-CTSA (UL1-RR024143) The Rockefeller University Center for Clinical and Translational Science.",
year = "2008",
month = jul,
doi = "10.1093/hmg/ddn122",
language = "אנגלית",
volume = "17",
pages = "2219--2227",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "14",
}