Association of variants of prodynorphin promoter 68-bp repeats in caucasians with opioid dependence diagnosis: Effect on 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 opioidexposed, 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

Current status of opioid addiction treatment and related preclinical research

“…A second group of gene variants that have been shown to be associated with different addictive diseases is the functional 68–base pair (bp) repeat present in one to four copies in the promoter of the prodynorphin ( PDYN ) gene, which encodes for the endogenous neuropeptide at κ-opioid receptors ( 94 ). Some studies have found an association of this polymorphism with aspects of opioid addiction ( 95 , 96 ) in Caucasian populations, and similar findings of association of the number of 68-bp repeats have been reported in studies of the genetic determinants of cocaine addiction ( 97 ).…”

Association between prodynorphin gene polymorphisms and opioid dependence susceptibility: a meta-analysis

“…First, the present outcomes were based on unadjusted estimates. Because raw data for confounding factors like age [30], gender [15], socioeconomic status [31] of the participants were unavailable, we could not perform the corresponding stratification analysis. Second, the number of participants of each included study was limited, thus lacking enough statistic power to guarantee the association.…”