Background: There is no countable biomarker for opioid dependence treatment responses thus far. In this study, we recruited Taiwanese methadone maintenance treatment (MMT) patients to search for genes involving the regulatory mechanisms of methadone dose by genome-wide association analyses. Methods: 344 Taiwanese MMT patients were included for a genome-wide association study. The involvement of GRK5 in opioid dependence was then further confirmed by gene expression study on lymphoblastoid cell lines derived from 3 independent age- and gender-matched groups, namely MMT patients, medication-free former heroin abusers, and normal controls. Results: The results indicated that GRK5, the gene encoding an enzyme related to mu-opioid receptor desensitization, is associated with methadone dose by additive model of gene-based association analysis (P=6.76x10-5). We found that 6 out of the 55 single nucleotide polymorphisms (SNPs) from the genome-wide genotype platform and 2 SNPs from the 29 additionally selected SNPs were significantly associated with methadone maintenance dose in both genotype and allele type (P</=0.006), especially in patients who were tested negative in the urine morphine test. The levels of GRK5 gene expression were similar between MMT patients and medication-free former heroin abusers. However, the normal controls showed a significantly lower level of GRK5 gene expression than the other groups (P=0.019). Conclusions: The results suggested an important role for GRK5 in the regulatory mechanisms of methadone dose and course of heroin dependence.
Date:
2018-10
Relation:
International Journal of Neuropsychopharmacology. 2018 Oct;21(10):910-917.
