Impact of SNP–SNP Interaction Among ABCB1 , ARRB2 , DRD1 and OPRD1 on Methadone Dosage Requirement in Han Chinese Patients

Aim: To evaluate the potential association of the genetic polymorphisms in ABCB1, ARRB2, DRD1 and OPRD1 genes with methadone dosage requirement among Han Chinese opioid-dependent patients. Materials & methods: Eight SNPs in ABCB1, ARRB2, DRD1 and OPRD1 genes were selected and genotyped using Sequenom MassARRAY platform among 257 methadone maintenance treatment patients. The required information about stable methadone dose, urine analysis for opioid and socio-demographic characteristics was collected. Generalized multifactor dimensionality reduction method was performed to analyze the SNP–SNP interaction. Results: We found that patients carrying the rs529520TG genotype of OPRD1 probably required higher methadone treatment dosage. A 3-locus SNP–SNP interaction pattern (rs1128503 in ABCB1, rs529520 in OPRD1 and rs1045280 in ARRB2) was significantly associated with the methadone dosage requirement (p = 0.029). Conclusion: Our results suggested that specific OPRD1 variants and interaction among polymorphisms in ABCB1, OPRD1 and ARRB2 genes contributes to methadone dosage requirement in Han Chinese opioid-dependent patients.