Ankyrin Repeat and Kinase Domain Containing 1 Gene, and Addiction Vulnerability

Abstract

The TaqIA single nucleotide variant (SNV) has been tested for association with addictions in a huge number of studies. TaqIA is located in the ankyrin repeat and kinase domain containing 1 gene (ANKK1) that codes for a receptor interacting protein kinase. ANKK1 maps on the NTAD cluster along with the dopamine receptor D2 (DRD2), the tetratricopeptide repeat domain 12 (TTC12) and the neural cell adhesion molecule 1 (NCAM1) genes. The four genes have been associated with addictions, although TTC12 and ANKK1 showed the strongest associations. In silico and in vitro studies revealed that ANKK1 is functionally related to the dopaminergic system, in particular with DRD2. In antisocial alcoholism, epistasis between ANKK1 TaqIA and DRD2 C957T SNVs has been described. This clinical finding has been supported by the study of ANKK1 expression in peripheral blood mononuclear cells of alcoholic patients and controls. Regarding the ANKK1 protein, there is direct evidence of its location in adult and developing central nervous system. Together, these findings of the ANKK1 gene and its protein suggest that the TaqIA SNV is a marker of brain differences, both in structure and in dopaminergic function, that increase individual risk to addiction development.

Motivational learning biases are differentially modulated by genetic determinants of striatal and prefrontal dopamine function

“…In addition, relative to A2 homozygotes, A1 carriers showed poorer performance in avoiding actions associated with punishment and lower activations of PFC and striatum during processing of negative feedback (Klein et al 2007;Frank and Hutchison, 2009;Jocham et al 2009). Furthermore, there is evidence of associations of the A1 allele with psychiatric disorders such as addictionsmost notably alcohol dependence (for a meta-analysis, see Wang et al 2013; for reviews, see Samochowiec et al 2014 andKoeneke et al 2020)-and ADHD (for a metaanalysis, see Pan et al 2015). In addition, it was initially hypothesized that there was an advantage of the A1 allele in schizophrenia disorders in terms of lower risk (Dubertret et al 2004) and better response to haloperidol (Schafer et al 2001).…”

“…Furthermore, there is evidence of associations of the A1 allele with psychiatric disorders such as addictions—most notably alcohol dependence (for a meta-analysis, see Wang et al 2013 ; for reviews, see Samochowiec et al 2014 and Koeneke et al 2020 )—and ADHD (for a meta-analysis, see Pan et al 2015 ). In addition, it was initially hypothesized that there was an advantage of the A1 allele in schizophrenia disorders in terms of lower risk (Dubertret et al 2004 ) and better response to haloperidol (Schafer et al 2001 ).…”

Investigating the association between common DRD2/ANKK1 genetic polymorphisms and schizophrenia: a meta-analysis

“…The association of DRD2, the target of all affective antipsychotic medications, with schizophrenia has also been corroborated by a genomewide association study, identifying DRD2 as one of the major risk genes for schizophrenia (Beaulieu and Gainetdinov 2011; Schizophrenia Working Group of the Psychiatric Genomics 2014). Ankyrin repeat and kinase domain containing 1 (ANKK1) is another gene that is closely associated with DRD2 and is closely related to dopaminergic signalling (Koeneke et al 2020). Taq1A, a polymorphism originally associated with DRD2 has recently been found to be located on the ANKK1 gene (Neville et al 2004).…”

Ankk1 Loss of Function Disrupts Dopaminergic Pathways in Zebrafish

“…ANKK1 maps to chromosome 338,400,418;GRCh38/hg38) in a 512 kb gene cluster that includes the neural cell adhesion molecule 1 (NCAM1), tetratricopeptide repeat domain 12 (TTC12) and dopamine receptor 2 (DRD2) genes (Neville et al, 2004;Mota et al, 2012). The NCAM-TTC12-ANKK1-DRD2 (NTAD) cluster is conserved among the vertebrates and has been proposed to be involved in neurogenesis and in the development of dopaminergic pathways (Yi et al, 2007;España-Serrano et al, 2017;Rubio-Solsona et al, 2018;Koeneke et al, 2020). In the adult mouse brain, ANKK1 protein is expressed in neural stem cells, in post-mitotic Abbreviations: III, oculomotor nerve; Cans, commissura ansulata; D, dorsal telencephalic area; Dc, central zone of D; Dd, dorsal zone of D; Dl, lateral zone of D; DIL, diffuse nucleus of the inferior lobe; Dm, medial zone of D; Dp, posterior zone of D; DV, descending trigeminal root; ECL, external cellular layer of olfactory bulb including mitral cells; GL, glomerular layer of olfactory bulb; Hd, dorsal hypothalamus; ICL, internal cellular layer of olfactory bulb; LLF, lateral longitudinal fascicle; PGZ, periventricular gray zone of the optic tectum; PPa, parvocellular preoptic nucleus, anterior part; TelV, telencephalic ventricle; TeO, optic tectum; Tl, torus longitudinalis; TLa, torus lateralis; TSc, central nucleus of torus semicircularis; TTB, tractus tectobulbaris; Val, lateral division of valvula cerebelli; Vam, medial division of valvula cerebelli; Vas, vascular lacuna of area postrema; Vd, dorsal nucleus of ventral telencephalic area; Vp, posterior nucleus of ventral telencephalic area; Vv, ventral nucleus of ventral telencephalic area.…”