Updated Findings of the Association and Functional Studies of DRD2/ANKK1 Variants with Addictions

Abstract

Both nicotine and alcohol addictions are severe public health hazards worldwide. Various twin and family studies have demonstrated that genetic factors contribute to vulnerability to these addictions; however, the susceptibility genes and the variants underlying them remain largely unknown. Of susceptibility genes investigated for addictions, DRD2 has received much attention. Considering new evidence supporting the association of DRD2 and its adjacent gene ankyrin repeat and kinase domain containing 1 (ANKK1) with various addictions, in this paper, we provide an updated view of the involvement of variants in DRD2 and ANKK1 in the etiology of nicotine dependence (ND) and alcohol dependence (AD) based on linkage, association, and molecular studies. This evidence shows that both genes are significantly associated with addictions; however the association with ANKK1 appears to be stronger. Thus, both more replication studies in independent samples and functional studies of some of these variants are warranted.

Meta-Analysis Reveals Significant Association of the 3′-UTR VNTR inSLC6A3with Alcohol Dependence

“…Further, functional magnetic resonance imaging (fMRI) studies on healthy subjects without any diagnosed mental disorders demonstrated that A9 homozygote or heterozygote carriers had a greater brain ventral striatal response to both anticipation and receipt of reward than that of A10 homozygote carriers (Dreher et al, 2009, Forbes et al, 2009). In addition, several meta-analyses, including the one recently reported by our group, have shown that the SLC6A3 VNTR is significantly associated with smoking cessation (Ma et al, 2015b) and various psychiatric disorders (Yang et al, 2007, Kambeitz et al, 2014), which are all correlated with AD (Ma et al, 2014, Li and Burmeister, 2009). Therefore, it is plausible to infer that the VNTR genotypes confer susceptibility to alcoholism.…”

“…Particularly, the dopaminergic mesocorticolimbic reward pathways have been linked to the pathogenesis of addictions, including alcoholism. Consequently, genes with a dopaminergic function have received much attention in relation to the etiology of AD and other addictions (Muramatsu and Higuchi, 1995, van der Zwaluw et al, 2009, Ma et al, 2014, Ma et al, 2015a). …”

DRD2 TaqI A polymorphism in Eastern Uttar Pradesh population

“…One of the most important system intervening reward mechanisms is considered to be dopaminergic pathways. Dopaminergic neurons are present in VTA of midbrain, projected into nucleus accumbens and ventral striatum [1] All the genes, involved in regulating the assembly of this system in brain is of great interest and can be a suitable candidate for investigation of molecular basis of addiction and several other psychiatric disorders [2]. Among these, the gene of interest that effect the dopaminergic neurotransmission is the Dopamine D2 receptor (DRD2) gene that is located at chromosome 11q22-23 encoding a G-Protein coupled receptor (Giinhibitory G protein) in post synaptic neurons [3] performing dual function of inhibitory auto receptor and a post synaptic receptors [4].…”

Genetic influences on delay discounting in smokers: examination of a priori candidates and exploration of dopamine-related haplotypes

“…This is because the SNP rs1800497 was previously believed to be located within the dopamine D 2 receptor gene ( DRD2 ), but is actually located in the adjacent ANKK1 gene. Although loci across several genes in this region ( NCAM1-TTC12-ANKK1-DRD2 ) are in high linkage disequilibrium (LD) (i.e., non-random associations among alleles; Mota et al 2012), this particular locus has been of focus due frequent association with addictive phenotypes and its putative role in the dopaminergic system (Ma et al 2015). Furthermore, positron emission tomography has revealed that rs1800497 is related to dopamine D 2 /D 3 receptor density (Thompson et al 1997; Pohjalainen et al 1998; Jönsson et al 1999; Savitz et al 2013).…”