Ankyrin repeat and kinase domain containing 1 (ANKK1) also known as protein kinase PKK2 or sugen kinase 288 (SgK288) is an enzyme that in humans is encoded by the ANKK1gene. The ANKK1 is a member of an extensive family of the Ser/Thr protein kinase family, and protein kinase superfamily involved in signal transduction pathways.
Clinical significance
This gene contains a single nucleotide polymorphism that causes an amino acid substitution within the 11th of 12 ankyrin repeats of ANKK1 (Glu713Lys of 765 residues). This polymorphism, which is commonly referred to Taq1A, was previously believed to be located in the promoter region of the DRD2 gene, since the polymorphism is proximal to the DRD2 gene and can influence DRD2 receptor expression.[5] It is now known to be located in the coding region of the ANKK1 gene which controls the synthesis of dopamine in the brain.[6] The A1 allele is associated with increased activity of striatalL-amino acid decarboxylase.[7]
Given that the A1+ allele is associated with antisocial personality disorder, one may infer that the allele is also associated with narcissistic personality disorder and histrionic personality disorder. However, these predictions have not yet been empirically verified.
A1+ genotype frequencies
European population estimates for A1+ genotype frequencies range from 20.8 to 43.4% (National Center of Biotechnology Information (NCBI), identification number rs1800497).[12]
Addictive behaviors
The ANKK1 gene is closely linked to dopamine receptor D2 (DRD2) on chromosome band 11q23.1.[13] The A1 allele of the Taq1A polymorphism (rs1800497T), is located ≈10kb downstream of the dopamine receptor DRD2 gene. Dopamine (DA) is a neurotransmitter in the brain, which controls feelings of wellbeing. This sensation results from the interaction of dopamine and other neurotransmitters such as serotonin, the opioids, and other brain chemicals. Dopamine increases the motivation for food cravings and appetite mediation.[14]
The Reward Deficiency Syndrome (RDS) involves the pleasures or reward mechanisms that rely on dopamine. The result of this deficiency is based on the genetic makeup; this helps explain how certain simple genetic anomalies can give rise to complex aberrant behaviours as the ones mentioned previously. The A1 allelic prevalence has been reported to be significantly higher in obese individuals than in lean subjects,[15] moreover, individuals with increased body mass index (BMI) (BMI >30 kg/m2) have fewer DRD2 dopamine receptors. Investigators have also suggested that hormonal mechanism may underline a gender difference in the ability to suppress hunger in relation to this SNP, which may contribute to the greater incidence of obesity in women compared to men.[16] However, authors have pointed out that A1 carriers have difficulty in learning from negative feedback in a reinforcement-learning task and are less efficient at learning to avoid actions that have negative consequences.
^Neville MJ, Johnstone EC, Walton RT (June 2004). "Identification and characterization of ANKK1: a novel kinase gene closely linked to DRD2 on chromosome band 11q23.1". Hum. Mutat. 23 (6): 540–5. doi:10.1002/humu.20039. PMID15146457. S2CID22242611.
^Laakso A, Pohjalainen T, Bergman J, Kajander J, Haaparanta M, Solin O, Syvälahti E, Hietala J (June 2005). "The A1 allele of the human D2 dopamine receptor gene is associated with increased activity of striatal L-amino acid decarboxylase in healthy subjects". Pharmacogenet. Genomics. 15 (6): 387–91. doi:10.1097/01213011-200506000-00003. PMID15900211. S2CID25424974.
^Lawford B, Young R, Noble EP, Crawford D, Rowell J, Shadforth S, Ritchie T, Zhang X, Cooksley GE (January 1999). "The DRD2A₁allele: a behavioural genetic risk factor in hepatitis C infection of persistent drug abusers". Addict Biol. 4 (1): 61–6. doi:10.1080/13556219971858. PMID20575771. S2CID5493559.
^Lu RB, Lee JF, Huang SY, Lee SY, Chang YH, Kuo PH, Chen SL, Chen SH, Chu CH, Lin WW, Wu PL, Ko HC (November 2010). "Interaction between ALDH2*1*1 and DRD2/ANKK1 TaqI A1A1 genes may be associated with antisocial personality disorder not co-morbid with alcoholism". Addict Biol. 17 (5): 865–874. doi:10.1111/j.1369-1600.2010.00268.x. PMID21070510. S2CID205400719.
^"rs1800497". Reference SNP(refSNP) Cluster Report. United States National Center for Biotechnology Information.
^Neville MJ, Johnstone EC, Walton RT (22 April 2004). "Identification and characterization of ANKK1: A novel kinase gene closely linked to DRD2 on chromosome band 11q23.1". Human Mutation. 23 (6): 540–545. doi:10.1002/humu.20039. PMID15146457. S2CID22242611.
