ABCB1 Polymorphisms in High-Dose and Low-Dose Dependent Patients Under Methadone Maintenance Treatment in an Iranian Population

Abstract

Background: Drug abuse is a major problem in Iran with a huge social burden. Methadone maintenance treatment (MMT) is offered as a harm reduction program to decrease the consequences of opioid drug dependence. Single nucleotide polymorphisms (SNPs) in the ABCB1 gene, encoding P-glycoprotein, have shown associations with drug uptake in the central nervous system (CNS). Objectives: We aimed to identify the frequency of ABCB1 SNPs and haplotypes in Iranian opioid-dependent patients and the link between ABCB1 haplotypes and P-glycoprotein function. Methods: We randomly selected 400 patients undergoing methadone treatment from the MMT clinics in Shahroud, Iran. Of these, 320 people qualified for the study were sorted according to their dose requirement. Individuals with a dose of greater than 100 mg/day and less than 60 mg/day were selected and divided into two groups. Blood samples were taken from 83 high-dose dependent (HDD) and 86 low-dose dependent (LDD) individuals. DNA was extracted and ABCB1 SNPs at the C1236T, C3435T, A61G, G1199A, and G2677T loci were detected using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). The haplotypes were obtained by the use of SNP analyzer version 2.0 software. Results: No significant differences were observed in allele and genotype frequencies of the SNPs between HDD and LDD groups. Eleven unique haplotypes were obtained, of which only the TTAGG haplotype showed a significant difference between the two populations (P = 0.030557, χ2 = 4.678). Linkage disequilibrium was observed at 1199, 1236, and 3435 loci. There were no significant differences in methadone dose requirement between different haplotypes or genotypes. Conclusions: Here, for the first time, we reported the frequency of ABCB1 SNPs in opioid-dependent people in Iran. Regarding the results, it seems that the use of these SNPs is not beneficial to predict and optimize the amount of drug requirement in Iranian society. However, further genotyping studies are required to decipher the impact of genetic variability on methadone dependence.