Association of variants of prodynorphin promoter 68-bp repeats in caucasians with opioid dependence diagnosis: Effect on age trajectory of heroin use. (21st June 2019)

• Record Type: Journal Article
• Authors: Yuferov, Vadim; Randesi, Matthew; Butelman, Eduardo R; van den Brink, Wim; Blanken, Peter; van Ree, Jan M; Ott, Jürg; Kreek, Mary Jeanne
• Is Part Of: Neuroscience letters. Volume 704(2019)
• Page Start: 100
• Page End: 105
• Publication Date: 2019-06-21
• Subjects: HAT heroin-assisted treatment, added to methadone maintenance -- HC Healthy controls -- KMSK Kreek-McHugh-Schluger-Kellogg scale of maximum exposure to specific drugs -- L "Long" 68-base PDYN pair repeats: 3 or 4 copies -- S "Short" 68-base PDYN pair repeats: 1 or 2 copies -- MMT methadone maintenance treatment -- NOD Non-dependent opioid users -- OD Opioid dependence diagnosis (by DSM-IV criteria) -- SUD substance use disorders -- PDYN Prodynorphin gene -- VNTR variable number tandem repeats; Opioid dependence -- Non-dependent opioid use -- Prodynorphin polymorphisms -- VNTR -- KMSK; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2019.03.038
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: The functional PDYN 68-base pair polymorphism affects transcription levels of the gene. We studied heroin use in Caucasians diagnosed with opioid dependence. PDYN genotype "SS + SL" was associated with earlier age trajectory of heroin use. Abstract: The dynorphin/kappa opioid receptor (Dyn/KOR) system is involved in reward processing and dysphoria/anhedonia. Exposure to mu-opioid receptor agonists such as heroin increases expression of the prodynorphin gene ( PDYN ) in the brain. In this study in a Caucasian cohort, we examined the association of the functional PDYN 68-bp repeat polymorphism with opioid use disorders. In this case-control study, 554 subjects with Caucasian ancestry (142 healthy controls, 153 opioid-exposed, but never opioid dependent, NOD, and 259 with an opioid dependence diagnosis, OD) were examined for association of the PDYN 68-bp repeats with the diagnosis of opioid dependence (DSM-IV criteria), with a dimensional measure of heroin exposure (KMSK scale), and age trajectory parameters of heroin use (age of heroin first use, and age of onset of heaviest use). The PDYN 68-bp repeat genotype (classified as: "short-short" [SS], "long-long" [LL], and "short-long" [SL], based on the number of repeats) was not associated with categorical opioid dependence diagnoses. However, the LL genotype was associated with later age of first heroin use than the SS + SL genotype (19 versus 18 years; p < 0.01). This was also confirmed by a significant positive correlation between the number of repeats and the age of first use of heroin, in volunteers with OD (Spearman r = 0.16; p = 0.01). This suggests that the functional PDYN 68-bp repeat genotype is associated with the age of first use of heroin in Caucasians diagnosed with opioid dependence.