ABCB1 haplotype and OPRM1 118A > G genotype interaction in methadone maintenance treatment pharmacogenetics

Daniel T Barratt1 Discipline of Pharmacology, School of Medical Sciences, University of Adelaide, Adelaide, South AustraliaCorrespondence[email protected]

Janet K Coller1 Discipline of Pharmacology, School of Medical Sciences, University of Adelaide, Adelaide, South Australia

Richard Hallinan2 The Byrne Surgery, Specialist Drug and Alcohol Practice, Redfern, New South Wales

Andrew Byrne2 The Byrne Surgery, Specialist Drug and Alcohol Practice, Redfern, New South Wales

Jason M White1 Discipline of Pharmacology, School of Medical Sciences, University of Adelaide, Adelaide, South Australia

David JR Foster3 Division of Health Sciences, Sansom Institute, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia

Andrew A Somogyi1 Discipline of Pharmacology, School of Medical Sciences, University of Adelaide, Adelaide, South Australia;4 Department of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide, South Australia, Australia

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Table 1 Subject demographic data

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Table 2 Comparison of methadone dose, (R)-methadone C_trough and dose-adjusted (R)-methadone C_trough between common ABCB1 haplotype combinations and OPRM1 genotypes of methadone maintenance therapy patients

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Figure 1 Influence of ABCB1 haplotype group on (A) methadone dose and (C) trough plasma (R)-methadone concentrations (C_trough) among OPRM1 wild-type (118A/A) subjects; and OPRM1 118A > G genotype on (B) methadone dose and (D) C_trough among ABCB1 AGCGC/AGTTT haplotype combination subjects.

Notes: Lines are medians. *P < 0.05, **P < 0.01 versus ABCB1 AGCGC/AGCGC haplotype group, ^†P < 0.05 OPRM1118A/A versus A/G,G/G genotype in ABCB1 AGCGC/AGTTT haplotype group.

Figure SA1 BanI restriction fragment patterns for 2677G > T genotyping.

Notes: bp: size of marker bands in base pairs; M: pUC19/HpaII DNA molecular weight marker; 1, negative control; 2, homozygous variant genotype (T/T) with 224 bp undigested polymerase chain reaction product; 3, heterozygous genotype (G/T) with 224 bp undigested + 198 bp digested fragment; and 4, homozygous wild-type genotype (G/G) with 198 bp digested fragment. 26 bp digested fragments not visible on gel.

Table SB1 Multiple linear regression models for estimation of methadone dose based on weight and ABCB1 and OPRM1 genetic variability

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Table SC1 Frequencies of ABCB1 haplotypesTable Footnote^a and OPRM1 118A > G minor allele and genotypes in opioid-dependent methadone maintenance treatment patients

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ABCB1 haplotype and OPRM1 118A > G genotype interaction in methadone maintenance treatment pharmacogenetics

Table 1 Subject demographic data

Table 2 Comparison of methadone dose, (R)-methadone C_trough and dose-adjusted (R)-methadone C_trough between common ABCB1 haplotype combinations and OPRM1 genotypes of methadone maintenance therapy patients

Table SB1 Multiple linear regression models for estimation of methadone dose based on weight and ABCB1 and OPRM1 genetic variability

Table SC1 Frequencies of ABCB1 haplotypesTable Footnote^a and OPRM1 118A > G minor allele and genotypes in opioid-dependent methadone maintenance treatment patients

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ABCB1 haplotype and OPRM1 118A > G genotype interaction in methadone maintenance treatment pharmacogenetics

Figures & data

Table 1 Subject demographic data

Table 2 Comparison of methadone dose, (R)-methadone Ctrough and dose-adjusted (R)-methadone Ctrough between common ABCB1 haplotype combinations and OPRM1 genotypes of methadone maintenance therapy patients

Table SB1 Multiple linear regression models for estimation of methadone dose based on weight and ABCB1 and OPRM1 genetic variability

Table SC1 Frequencies of ABCB1 haplotypesTable Footnotea and OPRM1 118A > G minor allele and genotypes in opioid-dependent methadone maintenance treatment patients

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Table 2 Comparison of methadone dose, (R)-methadone C_trough and dose-adjusted (R)-methadone C_trough between common ABCB1 haplotype combinations and OPRM1 genotypes of methadone maintenance therapy patients

Table SC1 Frequencies of ABCB1 haplotypesTable Footnote^a and OPRM1 118A > G minor allele and genotypes in opioid-dependent methadone maintenance treatment patients