ABSTRACT
Previous studies have shown significant associations between OPRK1 and susceptibility to opioid dependence and the relationships between libido dysfunction and insomnia among opium addicts who underwent methadone maintenance treatment. The authors investigated the single locus and haplotype association of rs997917, rs6985606, and rs6473797 with susceptibility to opioid addiction. Samples were selected among 202 healthy individuals and 202 opium addicts undergoing methadone maintenance treatment. Genomic DNA was extracted from the whole blood samples of all subjects through a salting out procedure. All three variants were genotyped in the studied subjects using Amplification Refractory Mutation System-Polymerase Chain Reaction (ARMS-PCR). The whole analysis process was performed using SNPAlyze and SPSS ver.20 software packages. According to the single locus analyses, rs997917 and rs6985606 represented significant associations with opium addiction under recessive (p = 0.0128) and co-dominant (p = 0.0001) inheritance models, respectively. The haplotypes C-T-C (Permutation p = 0.014) and C-T-T (Permutation p = 0.0002) were significantly associated with opioid dependence. Among methadone maintenance treatment individuals, rs997917 was significantly associated with insomnia in both allelic and genotypic levels (p = 0.0001 and p = 0.038, respectively). Furthermore, rs6985606 had the only significant association with the co-incidence of insomnia and libido dysfunction in the methadone maintenance treatment group (p = 0.038). The OPRK1 gene variants showed significant association with susceptibility to opioid dependence among Iranians.
Subject(s)
Genetic Predisposition to Disease/genetics , Methadone/therapeutic use , Opiate Substitution Treatment , Opioid-Related Disorders/drug therapy , Opioid-Related Disorders/genetics , Polymorphism, Single Nucleotide , Receptors, Opioid, kappa/genetics , Adolescent , Adult , Aged , Behavior, Addictive/drug therapy , Behavior, Addictive/genetics , Case-Control Studies , Genotype , Haplotypes , Humans , Iran , Male , Middle Aged , Opioid-Related Disorders/complications , Sexual Dysfunctions, Psychological/complications , Sexual Dysfunctions, Psychological/genetics , Sleep Initiation and Maintenance Disorders/complications , Sleep Initiation and Maintenance Disorders/genetics , Young AdultABSTRACT
Genetic association of rs678849 along with neuroimaging and biomarker phenotypes, parallel with the known involvements of the OPRD1 in drug abuse, provided additional support for targeting these receptors as potential therapeutic targets in both neurodegenerative diseases and neuropsychiactric disorders such as Alzheimer's disease. Samples were selected among 202 opium-addicted participants undergoing methadone treatment and 202 healthy controls. Genomic DNA of all subjects was extracted from whole blood samples through a Salting Out procedure. Four variants (rs678849, 2236857, 2236855, and 760589) were genotyped in the studied subjects using ARMS-PCR. The analysis was performed using SNPalyze and SPSS ver.20 software. According to single locus analysis, rs678849 under dominant model (p < 0.001), rs2236857 under recessive model (p = 0.006), and the two variants, rs2236855 and rs760589 under co-dominant model, showed significant contributions between groups (p = 0.001 and p = 0.009, respectively). rs2236855 was associated with the development of libido dysfunction in opium-addicted patients undergoing methadone treatment (p = 0.011). Through haplotype analyses, five haplotypes with frequency of more than 5% displayed significant association with opioid dependence in study participants. In conclusion, the four studied OPRD1 gene variants and their haplotypes can play important roles in susceptibility to opioid dependence.
