Genetic signatures of heroin addiction

Abstract

Heroin addiction is a complex psychiatric disorder with a chronic course and a high relapse rate, which results from the interaction between genetic and environmental factors. Heroin addiction has a substantial heritability in its etiology; hence, identification of individuals with a high genetic propensity to heroin addiction may help prevent the occurrence and relapse of heroin addiction and its complications. The study aimed to identify a small set of genetic signatures that may reliably predict the individuals with a high genetic propensity to heroin addiction. We first measured the transcript level of 13 genes (RASA1, PRKCB, PDK1, JUN, CEBPG, CD74, CEBPB, AUTS2, ENO2, IMPDH2, HAT1, MBD1, and RGS3) in lymphoblastoid cell lines in a sample of 124 male heroin addicts and 124 male control subjects using real-time quantitative PCR. Seven genes (PRKCB, PDK1, JUN, CEBPG, CEBPB, ENO2, and HAT1) showed significant differential expression between the 2 groups. Further analysis using 3 statistical methods including logistic regression analysis, support vector machine learning analysis, and a computer software BIASLESS revealed that a set of 4 genes (JUN, CEBPB, PRKCB, ENO2, or CEBPG) could predict the diagnosis of heroin addiction with the accuracy rate around 85% in our dataset. Our findings support the idea that it is possible to identify genetic signatures of heroin addiction using a small set of expressed genes. However, the study can only be considered as a proof-of-concept study. As the establishment of lymphoblastoid cell line is a laborious and lengthy process, it would be more practical in clinical settings to identify genetic signatures for heroin addiction directly from peripheral blood cells in the future study.

Construction and Analysis of Protein-Protein Interaction Network of Heroin Use Disorder

“…We have identified the susceptibility genes associated with HUD in our previous case-control studies 43 , 44 that included 124 Han Chinese men from Taiwan as the cases fulfilling the diagnostic criteria of HUD according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5), and 124 demographically similar patients as the controls getting regular medical checkups at a local medical center. The details of the 248 participants and the investigating methods are in the previous studies 43 , 44 .…”

Adult consequences of prenatal drug exposure

“…Twin studies show that 48–58% of the variation in liability to alcoholism is genetically modulated with certain genes (e.g. JUN, CEBPB, PRKCB, ENO2 or CEBPG) capable of predicting risk to heroin addiction with 85% accuracy in known drug users …”

“…JUN, CEBPB, PRKCB, ENO2 or CEBPG) capable of predicting risk to heroin addiction with 85% accuracy in known drug users. 42 Gestational drug exposure may represent the first hit to a susceptible, developing neurological system. Prenatal cannabis, for example, may interfere with the endocannabinoid system, an important modulator and influence of neurodevelopment until adulthood.…”

Oś MIF/CD74 jako cel terapii metforminą w podocytopatii cukrzycowej — rzeczywista praktyka kliniczna

“…Macrophage migration inhibitory factor (MIF), a pleiotropic inflammatory mediator, is quasi-constitutively expressed by a variety of different cells and tissues, including immune and nonimmune cells like podocyte, mesangial cells in kidney [7]. It is the only cytokine that is stored in the secretary cells and is thus secreted rapidly on stimulation of CD74, and it was the first membrane receptor for MIF that was discovered; meanwhile, MIF and its homolog D-dopachrome tautomerase are the only ligands of CD74 [8]. Current research in vitro demonstrates that MIF exerted proinflammatory effects in podocyte via the CD74 receptor under stimulation [9,10].…”