Impact of SNP-SNP interaction among ABCB1, ARRB2, DRD1 and OPRD1 on methadone dosage requirement in Han Chinese patients

Rui Luo; Xingyuan Li; Shasha Qin; Zhenzhou Luo; Xi Luo; Peiwu Hu; Zhisheng Liu; Xiangling Feng; Xingli Li

doi:10.2217/pgs-2017-0072

Impact of SNP-SNP interaction among ABCB1, ARRB2, DRD1 and OPRD1 on methadone dosage requirement in Han Chinese patients

Pharmacogenomics. 2017 Dec;18(18):1659-1670. doi: 10.2217/pgs-2017-0072. Epub 2017 Nov 27.

Authors

Rui Luo¹, Xingyuan Li², Shasha Qin³, Zhenzhou Luo⁴, Xi Luo⁵, Peiwu Hu⁶, Zhisheng Liu⁷, Xiangling Feng⁸, Xingli Li¹

Affiliations

¹ Department of Epidemiology & Health Statistics, Xiangya School of Public Health, Central South University, Changsha, Hunan, China.
² Supervision Office, Tanngshan Animal Health Inspection Institute, Tangshan, Hebei, China.
³ Department of STD/AIDS Prevention & Control, Hunan Province Center for Disease Control & Prevention, Changsha, Hunan, China.
⁴ Department of STD/AIDS Prevention & Control, Shenzhen Nanshan Center for Chronic Disease Control, Shenzhen, Guangdong, China.
⁵ Department of Nosocomial Infection Management, Southwest Hospital, Chongqing, China.
⁶ Department of Scientific Research, Xiangya Hospital, Central South University, Changsha, Hunan, China.
⁷ Evaluation & Quality Control Section, The Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
⁸ Center for Preventive Medicine Experiment, Xiangya School of Public Health, Central South University, Changsha, Hunan, China.

PMID: 29173032
DOI: 10.2217/pgs-2017-0072

Abstract

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.

Keywords: Han Chinese; SNP–SNP interaction; methadone dosage requirement.

MeSH terms

ATP Binding Cassette Transporter, Subfamily B / genetics
Adult
Analgesics, Opioid / adverse effects
Asian People / genetics*
Female
Genotype
Humans
Male
Methadone / administration & dosage*
Middle Aged
Opiate Substitution Treatment / methods
Opioid-Related Disorders / drug therapy
Opioid-Related Disorders / genetics
Polymorphism, Single Nucleotide / genetics*
Receptors, Dopamine D1 / genetics*
Receptors, Opioid, delta / genetics*
beta-Arrestin 2 / genetics*

Substances

ABCB1 protein, human
ARRB2 protein, human
ATP Binding Cassette Transporter, Subfamily B
Analgesics, Opioid
DRD1 protein, human
OPRD1 protein, human
Receptors, Dopamine D1
Receptors, Opioid, delta
beta-Arrestin 2
Methadone