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Janet Hoenicka - One of the best experts on this subject based on the ideXlab platform.
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regulatory rare variants of the dopaminergic gene ANKK1 as potential risk factors for parkinson s disease
Scientific Reports, 2021Co-Authors: Estela Perezsantamarina, Francesc Palau, Pedro J Garciaruiz, Dolores Martinezrubio, Mario Ezquerra, Irene Planavarro, Jorge Puente, Maria Jose Marti, Janet HoenickaAbstract:Parkinson’s disease (PD) is characterized by cerebral dopamine depletion that causes motor and cognitive deficits. The dopamine-related gene ANKK1 has been associated with neuropsychiatric disorders with a dopaminergic deficiency in the striatum. This study aims to define the contribution of ANKK1 rare variants in PD. We found in 10 out of 535 PD patients 6 ANKK1 heterozygous rare alleles located at the 5′UTR, the first exon, intron 1, and the nearby enhancer located 2.6 kb upstream. All 6 ANKK1 single nucleotide variants were located in conserved regulatory regions and showed significant allele-dependent effects on gene regulation in vitro. ANKK1 variant carriers did not show other PD-causing Mendelian mutations. Nevertheless, four patients were heterozygous carriers of rare variants of ATP7B gene, which is related to catecholamines. We also found an association between the polymorphic rs7107223 of the ANKK1 enhancer and PD in two independent clinical series (P = 0.007 and 0.021). rs7107223 functional analysis showed significant allele-dependent effects on both gene regulation and dopaminergic response. In conclusion, we have identified in PD patients functional variants at the ANKK1 locus highlighting the possible relevance of rare variants and non-coding regulatory regions in both the genetics of PD and the dopaminergic vulnerability of this disease.
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ANKK1 is found in myogenic precursors and muscle fibers subtypes with glycolytic metabolism
PLOS ONE, 2018Co-Authors: Estrella Rubiosolsona, Salvador Marti, J J Vilchez, Francesc Palau, Janet HoenickaAbstract:Ankyrin repeat and kinase domain containing 1 (ANKK1) gene has been widely related to neuropsychiatry disorders. The localization of ANKK1 in neural progenitors and its correlation with the cell cycle has suggested its participation in development. However, ANKK1 functions still need to be identified. Here, we have further characterized the ANKK1 localization in vivo and in vitro, by using immunolabeling, quantitative real-time PCR and Western blot in the myogenic lineage. Histologic investigations in mice and humans revealed that ANKK1 is expressed in precursors of embryonic and adult muscles. In mice embryos, ANKK1 was found in migrating myotubes where it shows a polarized cytoplasmic distribution, while proliferative myoblasts and satellite cells show different isoforms in their nuclei and cytoplasm. In vitro studies of ANKK1 protein isoforms along the myogenic progression showed the decline of nuclear ANKK1-kinase until its total exclusion in myotubes. In adult mice, ANKK1 was expressed exclusively in the Fast-Twitch muscles fibers subtype. The induction of glycolytic metabolism in C2C12 cells with high glucose concentration or treatment with berberine caused a significant increase in the ANKK1 mRNA. Similarly, C2C12 cells under hypoxic conditions caused the increase of nuclear ANKK1. These results altogether show a relationship between ANKK1 gene regulation and the metabolism of muscles during development and in adulthood. Finally, we found ANKK1 expression in regenerative fibers of muscles from dystrophic patients. Future studies in ANKK1 biology and the pathological response of muscles will reveal whether this protein is a novel muscle disease biomarker.
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The Addiction-Related Gene ANKK1 is Oppositely Regulated by D1R- and D2R-Like Dopamine Receptors
Neurotoxicity Research, 2016Co-Authors: Guillermo Ponce, M. A. Jiménez-arriero, Tomas Palomo, Adolfo Quiñones-lombraña, Noelia Guerra Martín-palanco, Estrella Rubio-solsona, Janet HoenickaAbstract:The ankyrin repeat and kinase domain containing 1 ( ANKK1 ) Taq IA polymorphism has been extensively studied as a marker of the gene for dopamine receptor D2 ( DRD2 ) in addictions and other dopamine-associated traits. In vitro mRNA and protein studies have shown a potential connection between ANKK1 and the dopaminergic system functioning. Here, we have investigated whether ANKK1 expression in the brain is regulated by treatment with dopaminergic agonists. We used quantitative RT-PCR of total brain and Western blots of specific brain areas to study ANKK1 in murine brain after dopaminergic treatments. We found that ANKK1 mRNA was upregulated after activation of D1R-like dopamine receptors with SKF38393 (2.660 ± 1.035-fold; t : 4.066, d f : 11, P = 0.002) and apomorphine (2.043 ± 0.595-fold; t : 3.782, d f : 8, P = 0.005). The D2R-like agonist quinelorane has no effect upon ANKK1 mRNA (1.004 ± 0.580-fold; t : 0.015, d f : 10, P = 0.9885). In contrast, mice treatment with the D2R-like agonists 7-OH-DPAT and aripiprazole caused a significant ANKK1 mRNA downregulation (0.606 ± 0.057-fold; t : 2.786, d f : 10, P = 0.02 and 0.588 ± 0.130-fold; t : 2.394, d f : 11, P = 0.036, respectively). With respect the ANKK1 proteins profile, no effects were found after SKF38393 ( t : 0.54, d f : 2, P = 0.643) and Quinelorane ( t : 0.286, d f : 8, P = 0.782) treatments. In contrast, the D2R-like agonist 7-OH-DPAT (±) caused a significant increment of ANKK1 in the striatum ( t : 2.718, d f : 7; P = 0.03) when compared to the prefrontal cortex. The activation of D1R-like and D2-R-like leads to opposite transcriptional regulation of ANKK1 by specific pathways.
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the ANKK1 drd2 locus is a genomic substrate for affective priming and recognition of angry faces
Brain and behavior, 2015Co-Authors: A Koeneke, Janet Hoenicka, Guillermo Ponce, Evelio HuertasAbstract:Introduction: Ankyrin repeat and kinase domain containing I (ANKK1) and dopamine D2 receptor (DRD2) genes have been associated with psychopathic traits in clinical samples. On the other hand, individuals high in psychopathy show reduced affective priming and deficits in facial expression recognition. We have hypothesized that these emotion-related cognitive phenomena are associated with TaqIA (rs18000497) SNP (single nucleotide polymorphism) of the ANKK1 gene and with C957T (rs6277) SNP of the DRD2 gene. Methods: We performed a genetic association analysis in 94 self-reported Caucasian healthy volunteers. The participants completed 144 trials of an affective priming task, in which primes and targets were emotional words. They also had to recognize 64 facial expressions of happiness, sadness, anger, and fear in an expression recognition task. Regarding the genetic analyses, TaqIA and C957T SNPs were genotyped. Results: We found that the C957T SNP TT genotype was associated with a stronger priming effect and a better recognition of angry expressions. No associations were found for the TaqIA SNP. In addition, in silico analysis demonstrated that C957T SNP is a marker of a regulatory sequence at the 5′ UTR of ANKK1 gene, thus suggesting the involvement of the whole ANKK1/DRD2 locus in cognitive-emotional processing. Conclusions: These results suggest that affective priming and recognition of angry facial expressions are endophenotypes that lie on the pathway between the ANKK1/DRD2 locus and some deviant phenotypes.
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The Addiction-Related Gene ANKK1 in Parkinsonian Patients with Impulse Control Disorder
Neurotoxicity Research, 2015Co-Authors: Janet Hoenicka, Guillermo Ponce, Pedro J. García-ruiz, Antonio Herranz, Dolores Martínez-rubio, Estela Pérez-santamarina, Francesc PalauAbstract:Impulse control disorders (ICDs) comprise a wide spectrum of abnormal behaviors frequently found in patients with Parkinson’s disease (PD) receiving antiparkinsonian treatment. Some ICDs share several essential features with substance use disorders. In this work, we have studied the addiction-related gene ankyrin repeat and kinase domain containing I ( ANKK1 ) in a sample of PD patients involved in a multicenter study on ICD. We carried out the Taq IA ANKK1 single-nucleotide polymorphism (SNP) genotyping in PD patients. Clinical assessment of ICD was performed using the Questionnaire for impulsive–compulsive disorders in PD. We found no association between Taq IA SNP and ICD in PD patients ( p = 0.565). However, when PD patients were grouped according the diagnosis of any ICD with a potentially addictive reinforcement (ICDARs), A1− Taq IA genotype showed significant association ( p = 0.036). No association was found for the presence of punding in PD patients ( p = 0.289). A logistic regression analysis confirmed the independent effect of the A1− genotype upon ICDARs (OR 8.76, 95 % CI 1.3–57.8, Wald = 5.805, p = 0.024). The Taq IA genotype A1− is associated to ICDAR in our sample and it may differentiate two types of disorders which are part of the ICD definition in PD patients.
Guillermo Ponce - One of the best experts on this subject based on the ideXlab platform.
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The Addiction-Related Gene ANKK1 is Oppositely Regulated by D1R- and D2R-Like Dopamine Receptors
Neurotoxicity Research, 2016Co-Authors: Guillermo Ponce, M. A. Jiménez-arriero, Tomas Palomo, Adolfo Quiñones-lombraña, Noelia Guerra Martín-palanco, Estrella Rubio-solsona, Janet HoenickaAbstract:The ankyrin repeat and kinase domain containing 1 ( ANKK1 ) Taq IA polymorphism has been extensively studied as a marker of the gene for dopamine receptor D2 ( DRD2 ) in addictions and other dopamine-associated traits. In vitro mRNA and protein studies have shown a potential connection between ANKK1 and the dopaminergic system functioning. Here, we have investigated whether ANKK1 expression in the brain is regulated by treatment with dopaminergic agonists. We used quantitative RT-PCR of total brain and Western blots of specific brain areas to study ANKK1 in murine brain after dopaminergic treatments. We found that ANKK1 mRNA was upregulated after activation of D1R-like dopamine receptors with SKF38393 (2.660 ± 1.035-fold; t : 4.066, d f : 11, P = 0.002) and apomorphine (2.043 ± 0.595-fold; t : 3.782, d f : 8, P = 0.005). The D2R-like agonist quinelorane has no effect upon ANKK1 mRNA (1.004 ± 0.580-fold; t : 0.015, d f : 10, P = 0.9885). In contrast, mice treatment with the D2R-like agonists 7-OH-DPAT and aripiprazole caused a significant ANKK1 mRNA downregulation (0.606 ± 0.057-fold; t : 2.786, d f : 10, P = 0.02 and 0.588 ± 0.130-fold; t : 2.394, d f : 11, P = 0.036, respectively). With respect the ANKK1 proteins profile, no effects were found after SKF38393 ( t : 0.54, d f : 2, P = 0.643) and Quinelorane ( t : 0.286, d f : 8, P = 0.782) treatments. In contrast, the D2R-like agonist 7-OH-DPAT (±) caused a significant increment of ANKK1 in the striatum ( t : 2.718, d f : 7; P = 0.03) when compared to the prefrontal cortex. The activation of D1R-like and D2-R-like leads to opposite transcriptional regulation of ANKK1 by specific pathways.
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the ANKK1 drd2 locus is a genomic substrate for affective priming and recognition of angry faces
Brain and behavior, 2015Co-Authors: A Koeneke, Janet Hoenicka, Guillermo Ponce, Evelio HuertasAbstract:Introduction: Ankyrin repeat and kinase domain containing I (ANKK1) and dopamine D2 receptor (DRD2) genes have been associated with psychopathic traits in clinical samples. On the other hand, individuals high in psychopathy show reduced affective priming and deficits in facial expression recognition. We have hypothesized that these emotion-related cognitive phenomena are associated with TaqIA (rs18000497) SNP (single nucleotide polymorphism) of the ANKK1 gene and with C957T (rs6277) SNP of the DRD2 gene. Methods: We performed a genetic association analysis in 94 self-reported Caucasian healthy volunteers. The participants completed 144 trials of an affective priming task, in which primes and targets were emotional words. They also had to recognize 64 facial expressions of happiness, sadness, anger, and fear in an expression recognition task. Regarding the genetic analyses, TaqIA and C957T SNPs were genotyped. Results: We found that the C957T SNP TT genotype was associated with a stronger priming effect and a better recognition of angry expressions. No associations were found for the TaqIA SNP. In addition, in silico analysis demonstrated that C957T SNP is a marker of a regulatory sequence at the 5′ UTR of ANKK1 gene, thus suggesting the involvement of the whole ANKK1/DRD2 locus in cognitive-emotional processing. Conclusions: These results suggest that affective priming and recognition of angry facial expressions are endophenotypes that lie on the pathway between the ANKK1/DRD2 locus and some deviant phenotypes.
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The Addiction-Related Gene ANKK1 in Parkinsonian Patients with Impulse Control Disorder
Neurotoxicity Research, 2015Co-Authors: Janet Hoenicka, Guillermo Ponce, Pedro J. García-ruiz, Antonio Herranz, Dolores Martínez-rubio, Estela Pérez-santamarina, Francesc PalauAbstract:Impulse control disorders (ICDs) comprise a wide spectrum of abnormal behaviors frequently found in patients with Parkinson’s disease (PD) receiving antiparkinsonian treatment. Some ICDs share several essential features with substance use disorders. In this work, we have studied the addiction-related gene ankyrin repeat and kinase domain containing I ( ANKK1 ) in a sample of PD patients involved in a multicenter study on ICD. We carried out the Taq IA ANKK1 single-nucleotide polymorphism (SNP) genotyping in PD patients. Clinical assessment of ICD was performed using the Questionnaire for impulsive–compulsive disorders in PD. We found no association between Taq IA SNP and ICD in PD patients ( p = 0.565). However, when PD patients were grouped according the diagnosis of any ICD with a potentially addictive reinforcement (ICDARs), A1− Taq IA genotype showed significant association ( p = 0.036). No association was found for the presence of punding in PD patients ( p = 0.289). A logistic regression analysis confirmed the independent effect of the A1− genotype upon ICDARs (OR 8.76, 95 % CI 1.3–57.8, Wald = 5.805, p = 0.024). The Taq IA genotype A1− is associated to ICDAR in our sample and it may differentiate two types of disorders which are part of the ICD definition in PD patients.
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the ANKK1 gene associated with addictions is expressed in astroglial cells and upregulated by apomorphine
Biological Psychiatry, 2010Co-Authors: Janet Hoenicka, Laura Espanaserrano, Miguel Angel Jimenezarriero, Adolfo Quinoneslombrana, Ximena Alvirabotero, Leonor Kremer, Rocio Perezgonzalez, Roberto Rodriguezjimenez, Guillermo Ponce, Tomas PalomoAbstract:Background Taq IA, the most widely analyzed genetic polymorphism in addictions, has traditionally been considered a gene marker for association with D2 dopamine receptor gene ( DRD2 ). Taq IA is located in the coding region of the ANKK1 gene that overlaps DRD2 and encodes a predicted kinase ANKK1. The ANKK1 protein nonetheless had yet to be identified. This study examined the ANKK1 expression pattern as a first step to uncover the biological bases of Taq IA-associated phenotypes. Methods Northern blot and quantitative reverse-transcriptase polymerase chain reaction analyses were performed to analyze the ANKK1 mRNA. To study ANKK1 protein expression, we developed two polyclonal antibodies to a synthetic peptides contained in the putative Ser/Thr kinase domain. Results We demonstrate that ANKK1 mRNA and protein were expressed in the adult central nervous system (CNS) in human and rodents, exclusively in astrocytes. ANKK1 mRNA level in mouse astrocyte cultures was upregulated by apomorphine, suggesting a potential relationship with the dopaminergic system. Developmental studies in mice showed that ANKK1 protein was ubiquitously located in radial glia in the CNS, with an mRNA expression pick around embryonic Day 15. This time expression pattern coincided with that of the Drd2 mRNA. On induction of differentiation by retinoic acid, a sequential expression was found in human neuroblastoma, where ANKK1 was expressed first, followed by that of DRD2 . An opposite time expression pattern was found in rat glioma. Conclusions Spatial and temporal regulation of the expression of ANKK1 suggest an involvement of astroglial cells in Taq IA-related neuropsychiatric phenotypes both during development and adult life.
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the ANKK1 kinase gene and psychiatric disorders
Neurotoxicity Research, 2009Co-Authors: Guillermo Ponce, Tomas Palomo, Miguel Angel Jimenezarriero, Rocio Perezgonzalez, M Aragues, R Rodriguezjimenez, Janet HoenickaAbstract:The TaqIA single nucleotide polymorphism (SNP, rs1800497), which is located in the gene that codes for the putative kinase ANKK1 (ANKK1) near the termination codon of the D2 dopamine receptor gene (DRD2; chromosome 11q22-q23), is the most studied genetic variation in a broad range of psychiatric disorders and personality traits. A large number of individual genetic association studies have found that the TaqIA SNP is linked to alcoholism and antisocial traits. In addition, it has also been related to other conditions such as schizophrenia, eating disorders, and some behavioral childhood disorders. The TaqIA A1 allele is mainly associated with addictions, antisocial disorders, eating disorders, and attention-deficit/hyperactivity disorders, while the A2 allele occurs more frequently in schizophrenic and obsessive-compulsive patients. Current data show that the TaqIA polymorphism may be a marker of both DRD2 and ANKK1 genetic variants. ANKK1 would belong to a family of kinases involved in signal transduction. This raises the question of whether signaling players intervene in the pathophysiology of psychiatric disorders. Basic research on the ANKK1 protein and its putative interaction with the D2 dopamine receptor could shed light on this issue.
Tomas Palomo - One of the best experts on this subject based on the ideXlab platform.
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the addiction related protein ANKK1 is differentially expressed during the cell cycle in neural precursors
Cerebral Cortex, 2017Co-Authors: Laura Espanaserrano, Noelia Guerra Martinpalanco, Ana Monteropedrazuela, Estela Perezsantamarina, Rebeca Vidal, Ines Garciaconsuegra, Elsa M Valdizan, Angel Pazos, Tomas Palomo, Miguel Angel JimenezarrieroAbstract:TaqIA is a polymorphism associated with addictions and dopamine-related traits. It is located in the ankyrin repeat and kinase domain containing 1 gene (ANKK1) nearby the gene for the dopamine D2 receptor (D2R). Since ANKK1 function is unknown, TaqIA-associated traits have been explained only by differences in D2R. Here we report ANKK1 studies in mouse and human brain using quantitative real-time PCR, Western blot, immunohistochemistry, and flow cytometry. ANKK1 mRNA and protein isoforms vary along neurodevelopment in the human and mouse brain. In mouse adult brain ANKK1 is located in astrocytes, nuclei of postmitotic neurons and neural precursors from neurogenic niches. In both embryos and adults, nuclei of neural precursors show significant variation of ANKK1 intensity. We demonstrate a correlation between ANKK1 and the cell cycle. Cell synchronization experiments showed a significant increment of ANKK1-kinase in mitotic cells while ANKK1-kinase overexpression affects G1 and M phase that were found to be modulated by ANKK1 alleles and apomorphine treatment. Furthermore, during embryonic neurogenesis ANKK1 was expressed in slow-dividing neuroblasts and rapidly dividing precursors which are mitotic cells. These results suggest a role of ANKK1 during the cell cycle in neural precursors thus providing biological support to brain structure involvement in the TaqIA-associated phenotypes.
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The Addiction-Related Gene ANKK1 is Oppositely Regulated by D1R- and D2R-Like Dopamine Receptors
Neurotoxicity Research, 2016Co-Authors: Guillermo Ponce, M. A. Jiménez-arriero, Tomas Palomo, Adolfo Quiñones-lombraña, Noelia Guerra Martín-palanco, Estrella Rubio-solsona, Janet HoenickaAbstract:The ankyrin repeat and kinase domain containing 1 ( ANKK1 ) Taq IA polymorphism has been extensively studied as a marker of the gene for dopamine receptor D2 ( DRD2 ) in addictions and other dopamine-associated traits. In vitro mRNA and protein studies have shown a potential connection between ANKK1 and the dopaminergic system functioning. Here, we have investigated whether ANKK1 expression in the brain is regulated by treatment with dopaminergic agonists. We used quantitative RT-PCR of total brain and Western blots of specific brain areas to study ANKK1 in murine brain after dopaminergic treatments. We found that ANKK1 mRNA was upregulated after activation of D1R-like dopamine receptors with SKF38393 (2.660 ± 1.035-fold; t : 4.066, d f : 11, P = 0.002) and apomorphine (2.043 ± 0.595-fold; t : 3.782, d f : 8, P = 0.005). The D2R-like agonist quinelorane has no effect upon ANKK1 mRNA (1.004 ± 0.580-fold; t : 0.015, d f : 10, P = 0.9885). In contrast, mice treatment with the D2R-like agonists 7-OH-DPAT and aripiprazole caused a significant ANKK1 mRNA downregulation (0.606 ± 0.057-fold; t : 2.786, d f : 10, P = 0.02 and 0.588 ± 0.130-fold; t : 2.394, d f : 11, P = 0.036, respectively). With respect the ANKK1 proteins profile, no effects were found after SKF38393 ( t : 0.54, d f : 2, P = 0.643) and Quinelorane ( t : 0.286, d f : 8, P = 0.782) treatments. In contrast, the D2R-like agonist 7-OH-DPAT (±) caused a significant increment of ANKK1 in the striatum ( t : 2.718, d f : 7; P = 0.03) when compared to the prefrontal cortex. The activation of D1R-like and D2-R-like leads to opposite transcriptional regulation of ANKK1 by specific pathways.
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the ANKK1 gene associated with addictions is expressed in astroglial cells and upregulated by apomorphine
Biological Psychiatry, 2010Co-Authors: Janet Hoenicka, Laura Espanaserrano, Miguel Angel Jimenezarriero, Adolfo Quinoneslombrana, Ximena Alvirabotero, Leonor Kremer, Rocio Perezgonzalez, Roberto Rodriguezjimenez, Guillermo Ponce, Tomas PalomoAbstract:Background Taq IA, the most widely analyzed genetic polymorphism in addictions, has traditionally been considered a gene marker for association with D2 dopamine receptor gene ( DRD2 ). Taq IA is located in the coding region of the ANKK1 gene that overlaps DRD2 and encodes a predicted kinase ANKK1. The ANKK1 protein nonetheless had yet to be identified. This study examined the ANKK1 expression pattern as a first step to uncover the biological bases of Taq IA-associated phenotypes. Methods Northern blot and quantitative reverse-transcriptase polymerase chain reaction analyses were performed to analyze the ANKK1 mRNA. To study ANKK1 protein expression, we developed two polyclonal antibodies to a synthetic peptides contained in the putative Ser/Thr kinase domain. Results We demonstrate that ANKK1 mRNA and protein were expressed in the adult central nervous system (CNS) in human and rodents, exclusively in astrocytes. ANKK1 mRNA level in mouse astrocyte cultures was upregulated by apomorphine, suggesting a potential relationship with the dopaminergic system. Developmental studies in mice showed that ANKK1 protein was ubiquitously located in radial glia in the CNS, with an mRNA expression pick around embryonic Day 15. This time expression pattern coincided with that of the Drd2 mRNA. On induction of differentiation by retinoic acid, a sequential expression was found in human neuroblastoma, where ANKK1 was expressed first, followed by that of DRD2 . An opposite time expression pattern was found in rat glioma. Conclusions Spatial and temporal regulation of the expression of ANKK1 suggest an involvement of astroglial cells in Taq IA-related neuropsychiatric phenotypes both during development and adult life.
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the ANKK1 kinase gene and psychiatric disorders
Neurotoxicity Research, 2009Co-Authors: Guillermo Ponce, Tomas Palomo, Miguel Angel Jimenezarriero, Rocio Perezgonzalez, M Aragues, R Rodriguezjimenez, Janet HoenickaAbstract:The TaqIA single nucleotide polymorphism (SNP, rs1800497), which is located in the gene that codes for the putative kinase ANKK1 (ANKK1) near the termination codon of the D2 dopamine receptor gene (DRD2; chromosome 11q22-q23), is the most studied genetic variation in a broad range of psychiatric disorders and personality traits. A large number of individual genetic association studies have found that the TaqIA SNP is linked to alcoholism and antisocial traits. In addition, it has also been related to other conditions such as schizophrenia, eating disorders, and some behavioral childhood disorders. The TaqIA A1 allele is mainly associated with addictions, antisocial disorders, eating disorders, and attention-deficit/hyperactivity disorders, while the A2 allele occurs more frequently in schizophrenic and obsessive-compulsive patients. Current data show that the TaqIA polymorphism may be a marker of both DRD2 and ANKK1 genetic variants. ANKK1 would belong to a family of kinases involved in signal transduction. This raises the question of whether signaling players intervene in the pathophysiology of psychiatric disorders. Basic research on the ANKK1 protein and its putative interaction with the D2 dopamine receptor could shed light on this issue.
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drd2 and ANKK1 genotype in alcohol dependent patients with psychopathic traits association and interaction study
British Journal of Psychiatry, 2008Co-Authors: G. Ponce, Janet Hoenicka, M Aragues, R Rodriguezjimenez, Evelio Huertas, M A Jimenezarriero, N Martinsune, Tomas PalomoAbstract:Background The TaqI-A polymorphism of the ANKK1 gene, adjacent to the DRD2 gene, has been associated with alcoholism and other psychiatric conditions, although other DRD2 gene variants, such as the C957T polymorphism, could be related to these phenotypic traits. Aims To investigate the contribution of the TaqI-A and the C957T polymorphisms to the presence of psychopathic traits in patients with alcoholism. Method We performed association and interaction analyses of the polymorphisms in 150 controls and 176 male alcohol-dependent patients assessed for the presence of dissocial personal disorder, using the Psychopathy Checklist–Revised (PCL–R). Results There was a significant association of the TaqI-A and C957T polymorphisms when both genotypes were present, with PCL–R scores of F 1-171=0.13 ( P =0.01) and a frequency of dissocial personal disorder OR=10.52, P <0.001. Conclusions The TaqI-A of the ANKK1 gene and the C957T of the DRD2 gene are epistatically associated with psychopathic traits in alcohol-dependent patients.
Martin Reuter - One of the best experts on this subject based on the ideXlab platform.
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on the genetics of loss aversion an interaction effect of bdnf val66met and drd2 ANKK1 taq1a
Behavioral Neuroscience, 2015Co-Authors: Gesine Voigt, Christian Montag, Sebastian Markett, Martin ReuterAbstract:Loss aversion is the tendency to overweight losses compared with gains in decision situations. Several studies have investigated the neurobiological background of this phenomenon and it was found that activation in the mesolimbic-mesocortical dopamine system during a gambling decision correlates with loss aversion. In a behavioral experiment with N = 143 subjects, the present study investigates the influence of 2 functional single-nucleotide polymorphisms on the BDNF gene (BDNF Val66Met polymorphism) and ANKK1 gene (DRD2 Taq1a/ANKK1 polymorphism), that are known to affect the dopamine system, on loss aversion. Additionally, associations of alexithymia, a personality construct describing the disability to consciously experience emotions in the self, with loss aversion and with the mentioned polymorphisms were assessed using the TAS-20 questionnaire, to replicate associations that have been reported before. Results revealed a significant interaction effect of the 2 polymorphisms on loss aversion. Carriers of the genetic constellation 66Met+/A1+ had the lowest loss aversion scores, compared with all other allelic groups. According to the literature this allelic configuration is characterized by a relatively low D2/3 receptor binding in the striatum and an impaired activity-dependent secretion of BDNF. This is the first study showing that loss aversion is related to naturally occurring differences in dopamine function.
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epistasis of the drd2 ANKK1 taq ia and the bdnf val66met polymorphism impacts novelty seeking and harm avoidance
Neuropsychopharmacology, 2010Co-Authors: Christian Montag, Christine Stelzel, Ulrike Basten, Christian J. Fiebach, Sebastian Markett, Turhan Canli, Martin ReuterAbstract:Mounting evidence from animal studies show that the mesolimbic dopaminergic pathways are modulated by the brain-derived neurotrophic factor (BDNF). This study investigates in N=768 healthy Caucasian participants the influence of two prominent functional single-nucleotide polymorphisms (SNPs) on the BDNF gene (BDNF Val66Met SNP) and the ankyrin repeat and kinase domain containing 1 (ANKK1) gene (DRD2 Taq Ia/ANKK1 SNP) on the personality traits of Novelty Seeking and Harm Avoidance, which are mediated, in part, through dopaminergic mesolimbic circuitry. Carriers of the 66Met+/A1+ variant scored lowest on Novelty Seeking and highest on Harm Avoidance, compared to all other genotype groups. These participants are characterized by a relatively low D2 receptor density in the striatum and an impaired activity-dependent secretion of BDNF. This is one of the first genetic association studies to show a modulatory role for BDNF genetic variation on genetically mediated differences in the mesolimbic dopaminergic system in the context of human personality.
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effects of dopamine related gene gene interactions on working memory component processes
European Journal of Neuroscience, 2009Co-Authors: Christine Stelzel, Ulrike Basten, Christian Montag, Martin Reuter, Christian J. FiebachAbstract:Dopamine modulates complex cognitive functions like working memory and cognitive control. It is widely accepted that an optimal level of prefrontal dopamine supports working memory performance. In the present study we used a molecular genetic approach to test whether the optimal activity of the dopamine system for different component processes of working memory is additionally related to the availability of dopamine D2 receptors. We sought evidence for this assumption by investigating the interaction effect (epistasis) of variations in two dopaminergic candidate genes: the catechol-O-methyltransferase (COMT) Val(158)Met polymorphism, which has been shown to influence prefrontal dopamine concentration, and the DRD2/ANKK1-Taq-Ia polymorphism, which has been related to the density of D2 receptors. Our results show that COMT effects on working memory performance are modulated by the DRD2/ANKK1-TAQ-Ia polymorphism and the specific working memory component process under investigation. Val- participants - supposedly characterized by increased prefrontal dopamine concentrations - outperformed Val+ participants in the manipulation of working memory contents, but only when D2 receptor density could be considered to be high. No such effect was present for passive maintenance of working memory contents or for maintenance in the face of distracting information. This beneficial effect of a balance between prefrontal dopamine availability and D2 receptor density reveals the importance of considering epistasis effects and different working memory subprocesses in genetic association studies.
Christian J. Fiebach - One of the best experts on this subject based on the ideXlab platform.
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epistasis of the drd2 ANKK1 taq ia and the bdnf val66met polymorphism impacts novelty seeking and harm avoidance
Neuropsychopharmacology, 2010Co-Authors: Christian Montag, Christine Stelzel, Ulrike Basten, Christian J. Fiebach, Sebastian Markett, Turhan Canli, Martin ReuterAbstract:Mounting evidence from animal studies show that the mesolimbic dopaminergic pathways are modulated by the brain-derived neurotrophic factor (BDNF). This study investigates in N=768 healthy Caucasian participants the influence of two prominent functional single-nucleotide polymorphisms (SNPs) on the BDNF gene (BDNF Val66Met SNP) and the ankyrin repeat and kinase domain containing 1 (ANKK1) gene (DRD2 Taq Ia/ANKK1 SNP) on the personality traits of Novelty Seeking and Harm Avoidance, which are mediated, in part, through dopaminergic mesolimbic circuitry. Carriers of the 66Met+/A1+ variant scored lowest on Novelty Seeking and highest on Harm Avoidance, compared to all other genotype groups. These participants are characterized by a relatively low D2 receptor density in the striatum and an impaired activity-dependent secretion of BDNF. This is one of the first genetic association studies to show a modulatory role for BDNF genetic variation on genetically mediated differences in the mesolimbic dopaminergic system in the context of human personality.
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effects of dopamine related gene gene interactions on working memory component processes
European Journal of Neuroscience, 2009Co-Authors: Christine Stelzel, Ulrike Basten, Christian Montag, Martin Reuter, Christian J. FiebachAbstract:Dopamine modulates complex cognitive functions like working memory and cognitive control. It is widely accepted that an optimal level of prefrontal dopamine supports working memory performance. In the present study we used a molecular genetic approach to test whether the optimal activity of the dopamine system for different component processes of working memory is additionally related to the availability of dopamine D2 receptors. We sought evidence for this assumption by investigating the interaction effect (epistasis) of variations in two dopaminergic candidate genes: the catechol-O-methyltransferase (COMT) Val(158)Met polymorphism, which has been shown to influence prefrontal dopamine concentration, and the DRD2/ANKK1-Taq-Ia polymorphism, which has been related to the density of D2 receptors. Our results show that COMT effects on working memory performance are modulated by the DRD2/ANKK1-TAQ-Ia polymorphism and the specific working memory component process under investigation. Val- participants - supposedly characterized by increased prefrontal dopamine concentrations - outperformed Val+ participants in the manipulation of working memory contents, but only when D2 receptor density could be considered to be high. No such effect was present for passive maintenance of working memory contents or for maintenance in the face of distracting information. This beneficial effect of a balance between prefrontal dopamine availability and D2 receptor density reveals the importance of considering epistasis effects and different working memory subprocesses in genetic association studies.