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Dopamine Transporter Gene (dopamine + transporter_gene)
Selected AbstractsDopamine transporter gene (DAT1) VNTR polymorphism in major psychiatric disorders: family-based association study in the Bulgarian populationACTA PSYCHIATRICA SCANDINAVICA, Issue 5 2002L. Georgieva Objective:,A 40-bp variable number tandem repeat in the 3,-UTR of dopamine transporter gene (DAT1) has been examined for association with major psychiatric disorders in several case,control studies. No significant results have been found. We used a new collection of parent,offspring trios to test for association with schizophrenia (SZ), bipolar 1 disorder (BPI) and schizoaffective (SA) disorder. Method:,We genotyped trios from Bulgarian origin where the proband had SZ (178 trios), BPI (77 trios) and SA (29 trios). Alleles ranging from 5 to 11 repeats were observed. The results were analysed with the extended TDT (ETDT). Results:,No preferential transmission of alleles was observed for any diagnostic group. The presence of allele DAT*10 was associated with the severity and frequency of auditory hallucinations, however, this result is not significant if corrected for multiple testing. Conclusion:,Our results are in agreement with previous reports of a lack of association between this polymorphism and major psychiatric disorders. [source] New insights on attention-deficit/hyperactivity disorder pharmacogenomicsDRUG DEVELOPMENT RESEARCH, Issue 3 2004Luis Augusto Rohde Abstract Although there is an impressive literature documenting both a strong participation of genetics in the etiology of attention-deficit/hyperactivity disorder (ADHD) and a high rate of response to stimulants and atomoxetine, surprisingly few studies on the pharmacogenomics of ADHD were conducted. This review aims to present a critical discussion of findings from recent investigations on this emerging new area of research. We performed a systematic computer review of the literature on ADHD pharmacogenomics. In addition, we contacted some research centers involved in research on ADHD genetics, asking for any kind of nonpublished data relevant for the topic of this revision. This review strategy identified only seven papers presenting nonduplicated research findings on ADHD pharmacogenomics. Contact with other investigators resulted in five more studies presented in medical meetings or still nonpublished. The majority of investigations are on dopaminergic genes, especially on polymorphisms at the dopamine transporter gene (DAT1). Although there were some instigating preliminary results suggesting the association between the homozygosity for the 10-repeat allele at DAT1 gene and response to methylphenidate, recent studies were not able to replicate these previous findings. Very few investigations addressed the role of nondopaminergic genes, or gene-to-gene interactions in ADHD pharmacogenomics. Pharmacogenomic studies of ADHD are in their infancy. We presented a discussion on the limitations and possible future directions of the research in the field. Drug Dev. Res. 62:172,179, 2004. © 2004 Wiley-Liss, Inc. [source] GENETIC STUDY: The interaction between the dopamine transporter gene and age at onset in relation to tobacco and alcohol use among 19-year-oldsADDICTION BIOLOGY, Issue 4 2009Brigitte Schmid ABSTRACT Recent evidence suggests that heterogeneity in the age at onset could explain the inconsistent findings of association studies relating the dopamine transporter (DAT1) gene with alcohol and nicotine consumption. The aim of this study was to examine interactions between two DAT1 polymorphisms and different initiation ages with regard to alcohol and tobacco consumption levels and dependence. Two hundred and ninety-one young adults (135 males, 156 females) participating in the Mannheim Study of Children at Risk were genotyped for the 40-bp variable number of tandem repeats (VNTR) and rs27072 polymorphisms of DAT1. Age at initiation was assessed at age 15 and 19 years. Information about current alcohol and tobacco consumption was obtained at age 19 years using self-report measures and structured interviews. Results suggest that age at onset of intensive consumption moderated the association of the DAT1 gene with early adult substance use and dependence, revealing a DAT1 effect only among individuals homozygous for the 10r allele of the 40-bp VNTR who had started daily smoking or being intoxicated early in life. Equally, carriers of the T allele of the rs27072 polymorphism reporting an early age at first intoxication showed higher current alcohol consumption at age 19 years. In contrast, no interaction between rs27072 and the age at first cigarette with regard to later smoking was observed. These findings provide evidence that the DAT1 gene interacts with an early heavy or regular drug exposure of the maturing adolescent brain to predict substance (ab)use in young adulthood. Further studies are required to confirm these findings. [source] Association of DRD4 polymorphism with severity of oppositional defiant disorder, separation anxiety disorder and repetitive behaviors in children with autism spectrum disorderEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2010Kenneth D. Gadow Abstract The objective was to examine whether a common polymorphism in the dopamine D4 receptor gene (DRD4) might be a potential biomarker for behavioral variation within the autism spectrum disorder clinical phenotype. Children (N = 66) were evaluated with a validated mother- and teacher-completed DSM-IV-referenced rating scale. Partial eta-squared (,p2) was used to gauge the magnitude of group differences: 0.01,0.06 = small, 0.06,0.14 = moderate and > 0.14 = large. Children who were 7-repeat allele carriers had more severe oppositional defiant disorder behaviors according to mothers' (,p2 = 0.10) and teachers' (,p2 = 0.06) ratings than noncarriers, but the latter was marginally significant (P = 0.07). Children who were 7-repeat allele carriers also obtained more severe maternal ratings of tics (,p2 = 0.07) and obsessions,compulsions (,p2 = 0.08). Findings for maternal ratings of separation anxiety were marginally significant (P = 0.08, ,p2 = 0.05). Analyses of combined DRD4 and dopamine transporter gene (DAT1) genotypes approached significance (P = 0.05) for teachers' ratings of oppositional behavior and mothers' ratings of tics. DRD4 allelic variation may be a prognostic biomarker for challenging behaviors in children with autism spectrum disorder, but these exploratory findings remain tentative pending replication with larger independent samples. [source] Improved association analyses of disease subtypes in case-parent triadsGENETIC EPIDEMIOLOGY, Issue 3 2006Michael P. Epstein Abstract The sampling of case-parent triads is an appealing strategy for conducting association analyses of complex diseases. In certain situations, one may have interest in using the triads to identify genetic variants that are associated with a specific subtype of disease, perhaps related to a characteristic cluster of symptoms. A straightforward strategy for conducting such a subtype analysis would be to analyze only those triads with the subtype of interest. While such a strategy is valid, we show that triads without the subtype of interest can provide additional genetic information that increases power to detect association with the subtype of interest. We incorporate this additional information using a likelihood-based framework that permits flexible modeling and estimation of allelic effects on disease subtypes and also allows for missing parental data. Using simulated data under a variety of genetic models, we show that our proposed association test consistently outperforms association tests that only analyze triads with the subtype of interest. We also apply our method to a triad study of attention-deficit hyperactivity disorder and identify a genetic variant in the dopamine transporter gene that is associated with a subtype characterized by extreme levels of both inattentive and hyperactive-impulsive symptoms. Genet. Epidemiol. 2006. © 2006 Wiley-Liss, Inc. [source] Association study of 5,-UTR polymorphisms of the human dopamine transporter gene with manic depressionBIPOLAR DISORDERS, Issue 5p1 2006Gerald Stöber Objectives:, To determine the degree of association of five single nucleotide polymorphisms at the 5,-untranslated region (5,-UTR) of the human dopamine transporter gene (hSLC6A3; hDAT1) in bipolar affective disorder. Methods:, In a case,control design study, the polymorphisms were genotyped for allelic and genotypic distribution between 105 index cases (50 males) with bipolar affective disorder according to DSM IV and 199 unaffected control subjects (120 males). Results:, At the 5,-UTR locus of hSLC6A3, no significant allelic or genotypic differences were observed between index cases and controls. However, distinct 5-locus genotypes accumulated in subjects with bipolar affective disorder compared to control subjects (p = 0.029, odds ratio 1.84, 95% confidence interval 1.12,3.02). Conclusions:, In conclusion, our data do not provide evidence for a major role of the 5,-UTR of the dopamine transporter gene in bipolar affective disorder. A minor contribution of distinct genotypes may be possible and warrants replication in extended samples. [source] | |||||||||||||