The association between the nicotinic acetylcholine receptor α4 subunit gene (CHRNA4) rs1044396 and Internet gaming disorder in Korean male adults

Abstract

The primary aim of this study was to investigate the genetic predisposition of Internet gaming disorder (IGD), and the secondary aim was to compare the results to those of alcohol dependence (AD). Two independent case-control studies were conducted. A total of 30 male participants with IGD, diagnosed according to the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, and 30 sex-matched controls participated in study 1. We designed targeted exome sequencing (TES) to test for 72 candidate genes that have been implicated in the pathogenesis of addiction. The genes included seven neurotransmitter (dopamine, serotonin, glutamate, r-aminobutyric acid (GABA), norepinephrine, acetylcholine, and opioid) system genes. A total of 31 male in-patients with AD and 29 normal male controls (NC) were enrolled in study 2. The same 72 genes included in study 1 and ten additional genes related to alcohol-metabolic enzyme were selected as the target genes, and we identified the genetic variants using the same method (TES). The IGD group had a lower frequency of the allele of rs1044396 in the nicotinic acetylcholine receptor alpha 4 subunit (CHRNA4), and this variant represents a protective allele against IGD. However, we did not find a significant difference in the polymorphisms of the 72 genes that encode neurotransmitter systems between the AD and NC groups. This study demonstrated that rs1044396 of CHRNA4 was significantly associated with IGD.

Brain and Cognition for Addiction Medicine: From Prevention to Recovery Neural Substrates for Treatment of Psychostimulant-Induced Cognitive Deficits

“…The role of nAChRs in impulsive behavior has been discussed previously (215). In humans, polymorphism in the α4 subunits of the nAChRs (CHRNA4) was associated with pathological gambling in Korean gamblers (216).…”

Neuropsychiatric factor and polymorphism gene in internet addiction

“…Impaired response inhibition is an important issue in behavioral addiction. These combined results suggest that the nicotinic acetylcholine receptor may play a role in IGD by modulating the dopaminergic pathway and may affect the addiction phenotype, such as response inhibition (Jeong et al, 2017).…”

Neurobiological Risk Factors for the Development of Internet Addiction in Adolescents

“…As was supported by numerous studies, the said genetic variants were also associated with a predisposition to depression—the most prevalent comorbid disorder in Internet-addictive subjects [64]. rs1044396 (nicotinic acetylcholine receptor subunit alpha 4 ( CHRNA4 ) gene): a small sized case-control study by Montag et al [65] showed the presence of an association with the CC genotype of the polymorphism rs1044396, which is also related to nicotine addiction and attention disturbances.rs2229910 (neurotrophic tyrosine kinase receptor type 3 ( NTRK3 ) gene): A pilot study by Jeong et al [66] was aimed at a specific exome and involved 30 adults with Internet addiction and 30 healthy subjects. The research included studying 83 polymorph regions and revealed statistically convincing associations with only one region: rs2229910.…”

“…rs2229910 (neurotrophic tyrosine kinase receptor type 3 ( NTRK3 ) gene): A pilot study by Jeong et al [66] was aimed at a specific exome and involved 30 adults with Internet addiction and 30 healthy subjects. The research included studying 83 polymorph regions and revealed statistically convincing associations with only one region: rs2229910.…”