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

The IA single nucleotide variant (SNV) has been tested for association with addictions in a huge number of studies. IA is located in the ankyrin repeat and kinase domain containing 1 gene () that codes for a receptor interacting protein kinase. maps on the NTAD cluster along with the dopamine receptor D2 (), the tetratricopeptide repeat domain 12 () and the neural cell adhesion molecule 1 () genes. The four genes have been associated with addictions, although and showed the strongest associations. In silico and in vitro studies revealed that is functionally related to the dopaminergic system, in particular with . In antisocial alcoholism, epistasis between IA and C957T SNVs has been described. This clinical finding has been supported by the study of 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 gene and its protein suggest that the IA SNV is a marker of brain differences, both in structure and in dopaminergic function, that increase individual risk to addiction development.