The effect of ANKK1 Taq1A and DRD2 C957T polymorphisms on executive function: A systematic review and meta-analysis

Abstract

Research in healthy adults suggests that C957T polymorphism of the dopamine D2 receptor encoding DRD2 and the Taq1A polymorphism of the neighbouring gene ankyrin repeat and kinase domain containing 1 (ANKK1) alter dopaminergic signalling and may influence prefrontally-mediated executive functions. A systematic review and meta-analysis was carried out on the evidence for the association of DRD2 C957T and ANKK1 Taq1A polymorphisms in performance on tasks relating to the three core domains of executive function: working memory, response inhibition and cognitive flexibility in healthy adults. CINAHL, MEDLINE, PsycARTICLES and PsychINFO databases were searched for predefined key search terms associated with the two polymorphisms and executive function. Studies were included if they investigated a healthy adult population with the mean age of 18-65 years, no psychiatric or neurological disorder and only the healthy adult arm were included in studies with any casecontrol design. Data from 17 independent studies were included in meta-analysis, separated by the Taq1A and C957T polymorphisms and by executive function tests: working memory (Taq1A, 6 samples, n=1270; C957T, 6 samples, n=977), cognitive flexibility (C957T, 3 samples, n=620), and response inhibition (C957T, 3 samples, n=598). The meta-analyses did not establish significant associations between these gene polymorphisms of interest and any of the executive function domains. Theoretical implications and methodological considerations of these findings are discussed.

Single Nucleotide Polymorphisms in Thyroid Hormone Transporter Genes MCT8, MCT10 and Deiodinase DIO2 Contribute to Inter-Individual Variance of Executive Functions and Personality Traits

“…Since the SNPs of MCT8, MCT10 and DIO2 are crucial for the function of thyroid hormones, we were interested if they would also influence cognitive functions and personality traits. There are numerous instances in which an influence of polymorphisms, mostly in monoaminergic genes, on both, cognitive processes [38][39][40][41] and personality traits [42][43][44][45] has been shown which motivated our approach. Previous studies have also shown that the amount of variance that can be explained by single polymorphisms is rather modest.…”

Association between the DRD2 TaqIA gene polymorphism and Parkinson disease risk: an updated meta-analysis

“…In PD, impaired reuptake of dopamine due to presynaptic neuronal degeneration, or postsynaptic dopamine receptor stimulation by a dopamine agonist may lead to a loss of the normal physiologic response. [36] Dopamine receptor D2 which is involved in working memory, response inhibition and cognitive flexibility, mainly distributed in the striatum, [37] is a protein that is encoded by the DRD2 gene in humans. This gene encodes the D2 subtype of the dopamine receptor, which is coupled to the Gi subtype of the G protein coupled receptor that inhibits adenylate cyclase activity.…”

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

“…Regarding TaqIA, previous reports found that A1 allele carriers have been related to worse working memory performance [82][83][84], or with less cognitive flexibility [82,85,86]. However, after meta-analysis, the signification was lost [81]. C957T SNV's previous positive association with working memory function [87][88][89], and response inhibition [87,88,90] were also negative after a meta-analysis, while cognitive flexibility was still associated.…”

“…The ANKK1/DRD2 locus has also been related to cognitive and emotional processes [73,80] that could be associated with risk for developing addictions. A recent systematic review and meta-analysis evaluated the association of ANKK1 TaqIA and DRD2 C957T SNVs in the performance of the executive functions in healthy adults [81]. Three main domains of executive functions were analyzed: response inhibition, cognitive flexibility and working memory.…”

“…C957T SNV's previous positive association with working memory function [87][88][89], and response inhibition [87,88,90] were also negative after a meta-analysis, while cognitive flexibility was still associated. Some of these inconsistencies could be attributed to both the heterogeneity of the executive function tasks used and the variability of the populations investigated [81]. Another source of heterogeneity, which might have contributed to the lack of significant findings, could be the differences in the grouping of the genotypes between studies.…”