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

Abstract

Genetic factors play an important role in the pathogenesis of schizophrenia. Dysregulations in the dopaminergic system have long been known to play an influential role in the development of this disorder. Although a large number of studies have investigated the association between genetic polymorphisms in the genes involved in this system and the risk of schizophrenia, the results have been inconsistent. In this meta-analysis, we searched for publications in Ovid Medline, Embase, Web of Science (science citation index expanded), and PsycNET for articles published until January 2020. We identified case-control studies investigating the association between four common genetic polymorphisms (rs6277, rs1799732, rs1800497, and rs1801028) and the risk of schizophrenia. The studies were subsequently selected according to the predefined inclusion and exclusion criteria. The data extraction was conducted according to the PRISMA guidelines. We also assessed the quality of the studies and investigated publication bias using funnel plot and Egger's regression test. The association analysis was conducted in allelic, dominant, and recessive genetic models. Subsequently, bioinformatics analysis of the effect of the polymorphisms found to be significantly associated with schizophrenia on protein stability, posttranslational modifications, and 3D protein structure was conducted. This meta-analysis showed that Taq1A (allelic model: OR, 0.856, 95% CI, 0.734-0.998) has a protective effect against the development of schizophrenia. Further, it was found that this variant may decrease ANKK1 protein stability. Further, this polymorphism was found to lead to the gain of modifications sites for ubiquitination (Ubi. score = -1.894) and methylation (Meth. score = -0.834). Several genetic factors contribute to the susceptibility of schizophrenia. The updated knowledge emerging from this meta-analysis showing the protective effect of rs1800497 polymorphism (Taq1A) can shed light on the role of Taq1A polymorphism in the susceptibility to schizophrenia and also pave way for further functional studies investigating the role of ANKK1 protein in the pathogenesis of schizophrenia.

Comparative and evolutionary analysis of RIP kinases in immune responses

“…Nevertheless, the domain structure of ANKK1 is highly similar to RIPK4 with an overall identity of 35% ( Meylan and Tschopp, 2005 ), which suggests that ANKK1 might have a function similar to RIPK4 in the induction of pro-inflammatory cytokines ( Meylan et al, 2002 ; Shin et al, 2008 ). ANKK1 is dominantly expressed in brain ( Supplementary Figure S1 ), which is consistent with the polymorphism Taq1A that leads to ANKK1 reduced stability being associated with schizophrenia ( Habibzadeh et al, 2021 ). However, immune cell expression by ImmGen ( Figure 2A ) does not include immune cells from the brain, such as microglia.…”

Athletic performance, sports experience, and exercise addiction: an association study on ANKK1 gene polymorphism rs1800497

“…The study further figured out that the individuals with A/A genotype were with lower levels of dopamine receptor, resulting in affected exercise habits ( Murakami et al, 2017 ). Recent studies have reported that individuals with the A/A or A/G genotype may be at higher risk for addictive behaviors, including exercise addiction, while those with the G/G genotype may have a lower risk for addictive behaviors ( Aliasghari et al, 2021 ; Habibzadeh et al, 2021 ; Switala and Leonska-Duniec, 2021 ; Switala et al, 2022 ).…”

“…The allele A has previously been associated to the altered cognitive behavioral capacity by changes in D2 receptor expression ( Thompson et al, 1997 ; Lachowicz et al, 2020 ; Antrobus et al, 2022a , b ). Moreover, the genotypes A/A and G/A have been linked to higher risk of certain neuropsychiatric disorders including schizophrenia and emotional eating habits, and obesity and alcohol, nicotine, and drug addiction ( Aliasghari et al, 2021 ; Habibzadeh et al, 2021 ; Switala and Leonska-Duniec, 2021 ; Switala et al, 2022 ). Nevertheless, further studies are needed to comprehensively understand the relationship between this variant and the athletic parameters.…”

Insights into the Promising Prospect of G Protein and GPCR-Mediated Signaling in Neuropathophysiology and Its Therapeutic Regulation

“…In the light of the pivotal role of D2 receptors in the pharmacological action of antipsychotics, numerous investigators have looked into the role of D2 receptor polymorphisms in schizophrenia. Several studies, that have included different groups of independent investigators undertaking metaexaminations, have reported a positive relationship between polymorphisms and schizophrenia related to the D2 receptor Ser311Cys [ 96 – 99 ]. Nonetheless, other evaluations have found no connections [ 99 ].…”