Significant association of <i>DRD2</i> and <i>ANKK1</i> genes with rural heroin dependence and relapse in men

Abstract

Introduction. Substance abuse significantly influences human health and may induce problems with social functioning worldwide. Numerous genetic and environmental risk factors, as well as their interactions, accelerate the development of drug addiction. Etiologically, the dopaminergic mesocorticolimbic reward pathways are related to psychoactive substance addiction, and the reward properties of heroin are connected with changes in the mesolimbic dopaminergic system. Objective. The aim of this study is a haplotypic analysis of subjects addicted to polysubstance. However, with the knowledge that this is not a homogenous subgroup, it was decided to separate and analyze homogenous subgroups of subjects in order to find specific haplotypic variants among them. The subjects in the subgroups were addicted to heroin, and subjects with more than two relapses in the past two years. Materials and method. The study group comprised of 301 polysubstance addicted rural male subjects. From this group, 2 homogenous subgroups of subjects were isolated and additionally analyzed: (1) a group of heroin addicted subjects (n=61), and (2) a group of heroin-addicted subjects with at least two relapses in the last two years (n=21). The group consisting of all polysubstance addicted rural subjects and both homogenous subgroups were analyzed against a control group of non-addicted subjects (n=300), matching gender and age. Five polymorphisms in the DRD2/ANKK1 region were analyzed: rs1076560, rs1800498, rs1079597, rs6276 in the DRD2 gene, and rs1800497 in the ANKK1 gene. Results. A statistically significant haplotype association was found in analysis of the heroin addicted subjects, compared to controls, and two possible trends -when comparing the whole group of addicted subjects to controls, and in relapse subgroups, compared to the controls. Conclusion.The results obtained showed that haplotypes indicate a part of the biological component of addiction.

Associated and intermediate factors between genetic variants of the dopaminergic D2 receptor gene and harmful alcohol use in young adults

“… 16 However, the significant association was observed more specifically for DRD2 rs1800498, which has, to our knowledge, never been found to be associated with AUD before. Indeed, although several studies found an association between this SNP and drug use disorders such as cannabis and heroin dependence, 13 , 15 the only study assessing the role of DRD2 rs1800498 in AUD reported a non‐significant result. 41 Nevertheless, this study differed from ours because it was conducted in patients who met the diagnosis of alcohol dependence, whereas in our larger and population‐based sample, subjects with either alcohol dependence or harmful alcohol use were considered cases.…”

“…[8][9][10] These SNPs have also been involved in other psychiatric diseases and drug use disorders. 11,12 Similarly, other studies reported a role of ANKK1 rs4938015 C allele and DRD2 rs1800498 A allele in drug use disorders such as cannabis and opiates, [13][14][15] thereby highlighting the role of these two genes in the broader concept of addiction.…”

Athletic performance, sports experience, and exercise addiction: an association study on ANKK1 gene polymorphism rs1800497

“…In addition to the listed genes, ANKK1 rs1800497 polymorphism influences cognitive behavioral capacity by the modulation of expression of D2 receptors (Thompson et al, 1997). Thus, this polymorphism has been included in the group of key variants involved in the process of addiction (Lachowicz et al, 2020). Moreover, some studies have emphasized that exercise addiction was associated with athletic performance.…”

“…ANKK1 c.2137G > A (rs1800497) polymorphism was further shown to associate with the addiction specifically. The allele A has previously been associated to the altered cognitive behavioral capacity by changes in D2 receptor expression (Thompson et al, 1997;Lachowicz et al, 2020;Antrobus et al, 2022a,b). Moreover, the genotypes A/A and G/A have been linked to higher risk of certain neuropsychiatric disorders including schizophrenia and emotional eating habits, and obesity and alcohol, nicotine, and drug addiction (Aliasghari et al, 2021;Habibzadeh et al, 2021;Switala and Leonska-Duniec, 2021;Switala et al, 2022).…”