APBB2, amyloid beta (A4) precursor protein-binding family B member 2 has been reported to be associated with opioid dependence. Dr. Yu-Li Liu from the Center for Neuropsychiatric Research reported the first time that the genetic variants in the APBB2 gene were associated with use of amphetamine in opioid dependent patients undergoing methadone maintenance treatment (MMT).
Dr. Liu and the team recruited 344 heroin-dependent patients undergoing MMT and assessed for use of amphetamine and opioids by urine toxicology, withdrawal severity, and side effects. DNAs were genome-widely genotyped for all patients. Single nucleotide polymorphisms (SNPs) in APBB2 were then selected for association analyses for methadone treatment responses. Gene expression levels of APBB2 were measured by real-time polymerase chain reaction (PCR) in the Epstein–Barr virus (EBV)-transformed lymphoblastoids from patients.
The team found MMT patients who used amphetamine showed a significantly higher percentage of positive results in the urine morphine test (P=0.005), and insomnia (P=0.018). In single locus association analyses, SNPs rs3935357 and rs4861075 located at intron 6 were significantly associated with amphetamine use in both genotype and allele type (general linear model (GLM), P=0.0003, and 0.0002 for genotype, and 0.0003, and 0.002 for allele type, respectively). The major allele type carriers had twice risk of amphetamine use compared to the minor allele type carriers. Subjects with the TT genotype of rs4861075 showed significantly higher levels of APBB2 gene expression in both total (P=0.02) and long-form (P=0.037) than those with CC genotype. Detailed mechanisms underlying the association of APBB2 with amphetamine use and level of plasma amyloid beta in MMT patients require further investigation. This finding has been published in Progress in Neuro-Psychopharmacology and Biological Psychiatry (2018 Jan 10;83:92-98).
Citation: Liu, CC; Fang, CP; Liu, TH Kuo, HW; Liu, SC; Wang, SC; Chen, ACH; Liu, YL. APBB2 is associated with amphetamine use and plasma beta-amyloids in patients receiving methadone maintenance treatment. Progress in Neuro-Psychopharmacology and Biological Psychiatry. 2018 Jan 10;83:92-98.