Dataset Information

Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence.

ABSTRACT: BACKGROUND:Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence. METHODS:Genetic information from four subject groups was collected: non-dependent opioid users (NOD) [n=163]; opioid-dependent (OD) patients in methadone maintenance treatment (MMT) [n=143]; opioid-dependent MMT-resistant patients in heroin-assisted treatment (HAT) [n=138]; and healthy controls with no history of opioid use (HC) [n=153]. Eighty-two variants in eight opioid system genes were studied. To establish the role of these genes in (a) non-dependent opioid use, and (b) heroin dependence, the following groups were compared: HC vs. NOD; HC vs. OD (MMT+HAT); and NOD vs. OD (MMT+HAT). RESULTS:Five unique SNPs in four genes showed nominally significant associations with non-dependent opioid use and heroin dependence. The association of the delta opioid receptor (OPRD1) intronic SNP rs2236861 with non-dependent opioid use (HC vs. NOD) remained significant after correction for multiple testing (OR=0.032; pcorrected=0.015). This SNP exhibited a significant gene-gene interaction with prepronociceptin (PNOC) SNP rs2722897 (OR=5.24; pcorrected=0.041) (HC vs. NOD). CONCLUSIONS:This study identifies several new and some previously reported associations of variants with heroin dependence and with non-dependent opioid use, an important and difficult to obtain group not extensively studied previously. Further studies are warranted to confirm and elucidate the potential roles of these variants in the vulnerability to illicit drug use and drug addiction.

SUBMITTER: Randesi M

PROVIDER: S-EPMC6842569 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence.

Randesi Matthew M van den Brink Wim W Levran Orna O Blanken Peter P Butelman Eduardo R ER Yuferov Vadim V da Rosa Joel Correa JC Ott Jurg J van Ree Jan M JM Kreek Mary Jeanne MJ

Drug and alcohol dependence 20160905

<h4>Background</h4>Heroin addiction is a chronic, relapsing brain disease. Genetic factors are involved in the development of drug addiction. The aim of this study was to determine whether specific variants in genes of the opioid system are associated with non-dependent opioid use and heroin dependence.<h4>Methods</h4>Genetic information from four subject groups was collected: non-dependent opioid users (NOD) [n=163]; opioid-dependent (OD) patients in methadone maintenance treatment (MMT) [n=143 ...[more]

PMID: 27664554

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Project description:BACKGROUND:Opioid dependence is a major health concern across the world and does also occur in adolescents. While opioid substitution treatment (OST) has been thoroughly evaluated in adult populations, very few studies have examined its use in adolescents. There are concerns that OST is underutilised in adolescents with heroin dependence. We sought to measure changes in drug use among adolescents receiving OST and also to examine treatment attrition during the first 12 months of this treatment. METHODS:We included all heroin dependent patients aged under 18.5 years commencing OST at one outpatient multidisciplinary adolescent addiction treatment service in Dublin, Ireland. Psycho-social needs were also addressed during treatment. Drug use was monitored by twice weekly urine drugs screens (UDS). Change in the proportion of UDS negative for heroin was examined using the Wilcoxon signed rank test. Attrition was explored via a Cox Regression multivariate analysis. RESULTS:OST was commenced by 120 patients (51% female and mean age 17.3 years). Among the 39 patients who persisted with OST until month 12, heroin abstinence was 21% (95% confidence interval [CI]?=?9-36%) at month three and it was 46% (95% CI?=?30-63%) at month 12. Heroin use declined significantly from baseline to month three (p?<?0.001) and from month three to month 12 (p?=?0.01). Use of other drugs did not change significantly. People using cocaine during month 12 were more likely to be also using heroin (p?=?0.02). Unplanned exit occurred in 25% patients by 120 days. The independent predictors of attrition were having children, single parent family of origin, not being in an intimate relationship with another heroin user and evidence of cocaine use just before treatment entry. CONCLUSIONS:We found that heroin dependent adolescent patients achieved significant reductions in heroin use within three months of starting OST and this improved further after a year of treatment, about half being heroin abstinent at that stage. Patient drop out from treatment remains a challenge, as it is in adults. Cocaine use before and during treatment may be a negative prognostic factor.

Project description:ImportanceThere is concern that nonmedical prescription opioid use is associated with an increased risk of later heroin use initiation in adolescents, but to our knowledge, longitudinal data addressing this topic are lacking.ObjectiveTo determine whether nonmedical prescription opioid use is associated with subsequent initiation of heroin use in adolescents.Design, setting, and participantsThis prospective longitudinal cohort study conducted in 10 high schools in Los Angeles, California, administered 8 semiannual surveys from 9th through 12th grade that assessed nonmedical prescription opioid use, heroin use, and other factors from October 2013 to July 2017. Students were baseline never users of heroin recruited through convenience sampling. Cox regression models tested nonmedical prescription opioid use statuses at survey waves 1 through 7 as a time-varying and time-lagged regressor and subsequent heroin use initiation across waves 2 to 8 as the outcome.ExposuresSelf-reported nonmedical prescription opioid use (past 30-day [current] use vs past 6-month [prior] use without past 30-day use vs no past 6-month use) at each wave from 1 to 7.Main outcomes and measuresSelf-reported heroin use initiation (yes/no) during waves 2 to 8.ResultsOf 3298 participants, 1775 (53.9%) were adolescent girls, 1563 (48.3%) were Hispanic, 548 (17.0%) were Asian, 155 (4.8%) were African American, 529 (16.4%) were non-Hispanic white, and 220 (6.8%) were multiracial. Among baseline never users of heroin in ninth grade with valid data (3298 [97% of cohort enrollees]; mean [SD] age, 14.6 [0.4] years), the number of individuals with outcome data available at each follow-up ranged from 2987 (90.6%) to 3200 (97.0%). The mean per-wave prevalence of prior and current nonmedical prescription opioid use from waves 1 to 7 was 1.9% and 2.7%, respectively. Seventy students (2.1%) initiated heroin use during waves 2 to 8. Prior vs no (hazard ratio, 3.59; 95% CI, 2.14-6.01; P < .001) and current vs no (hazard ratio, 4.37; 95% CI, 2.80-6.81; P < .001) nonmedical prescription opioid use were positively associated with subsequent heroin use initiation. For no, prior, and current nonmedical prescription opioid use statuses at waves 1 to 7, the estimated cumulative probabilities of subsequent heroin use initiation by wave 8 (42-month follow-up) were 1.7%, 10.7%, and 13.1%, respectively. In covariate-adjusted models, associations were attenuated but remained statistically significant and current nonmedical prescription opioid use risk estimates were stronger than corresponding associations of nonopioid substance use with subsequent heroin use initiation.Conclusions and relevanceNonmedical prescription opioid use was prospectively associated with subsequent heroin use initiation during 4 years of adolescence among Los Angeles youth. Further research is needed to understand whether this association is causal.

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Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence.

Publications

Variants of opioid system genes are associated with non-dependent opioid use and heroin dependence.

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