Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children

The search for genetic factors predisposing to Attention Deficit Hyperactivity Disorder (ADHD) has focused on genes that regulate dopaminergic pathways such as dopamine receptors and enzymes that regulate levels of dopamine in the synapse. There have been several reports of association between ADHD...

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Veröffentlicht in:Molecular psychiatry 2000-07, Vol.5 (4), p.396-404
Hauptverfasser: TAHIR, E, YAZGAN, Y, CIRAKOGLU, B, OZBAY, F, WALDMAN, I, ASHERSON, P. J
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container_end_page 404
container_issue 4
container_start_page 396
container_title Molecular psychiatry
container_volume 5
creator TAHIR, E
YAZGAN, Y
CIRAKOGLU, B
OZBAY, F
WALDMAN, I
ASHERSON, P. J
description The search for genetic factors predisposing to Attention Deficit Hyperactivity Disorder (ADHD) has focused on genes that regulate dopaminergic pathways such as dopamine receptors and enzymes that regulate levels of dopamine in the synapse. There have been several reports of association between ADHD and polymorphic variants within or near DRD4, DRD5, DAT1, DBH and COMT. In this study we set out to investigate specific alleles of DRD4 and DRD5, previously reported to be associated with ADHD, in a sample of Turkish children with DSM-IV ADHD children, as well as their relation to methylphenidate response and dimensional measures of symptom domains. One hundred and four independent trios and seven dyads were analysed using the transmission disequilibrium test (TDT). We found increased transmission of the DRD4 7-repeat allele (DRD4*7) (TDT chi2 = 2.79, P = 0.047). Given that we were testing specific a priori hypotheses regarding the associated alleles, we have used one-tailed P-values throughout. There was evidence of an interaction with methlyphenidate (MPH) response and analysis of the sample excluding non-responders revealed more significant evidence for the association (TDT chi2 = 4.48, P = 0.017). We also detected a trend for linkage and association in the DRD5 polymorphism (TDT chi2 = 2. 38, P = 0.06). Similar findings were obtained in relation to MPH response as analysis of MPH responders alone gave rise to a more significant association than that of the group as a whole (TDT chi2 = 4.9, P = 0.013). t-Test and logistic regression TDT analyses of DRD4*7 transmission with respect to dimensional rating scales of hyperactivity and impulsivity showed an inverse relation suggesting that in this sample DRD4*7 is associated with a lower level of ADHD symptomatology. While this may be due to stratification along a dimension of severity such that severe cases belong to a more extreme group with other specific genetic and environmental causes, similar to the model for low cognitive ability, it is more likely the result of a chance selection bias in this sample.
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Similar findings were obtained in relation to MPH response as analysis of MPH responders alone gave rise to a more significant association than that of the group as a whole (TDT chi2 = 4.9, P = 0.013). t-Test and logistic regression TDT analyses of DRD4*7 transmission with respect to dimensional rating scales of hyperactivity and impulsivity showed an inverse relation suggesting that in this sample DRD4*7 is associated with a lower level of ADHD symptomatology. 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J</creatorcontrib><title>Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><description>The search for genetic factors predisposing to Attention Deficit Hyperactivity Disorder (ADHD) has focused on genes that regulate dopaminergic pathways such as dopamine receptors and enzymes that regulate levels of dopamine in the synapse. There have been several reports of association between ADHD and polymorphic variants within or near DRD4, DRD5, DAT1, DBH and COMT. In this study we set out to investigate specific alleles of DRD4 and DRD5, previously reported to be associated with ADHD, in a sample of Turkish children with DSM-IV ADHD children, as well as their relation to methylphenidate response and dimensional measures of symptom domains. One hundred and four independent trios and seven dyads were analysed using the transmission disequilibrium test (TDT). We found increased transmission of the DRD4 7-repeat allele (DRD4*7) (TDT chi2 = 2.79, P = 0.047). Given that we were testing specific a priori hypotheses regarding the associated alleles, we have used one-tailed P-values throughout. There was evidence of an interaction with methlyphenidate (MPH) response and analysis of the sample excluding non-responders revealed more significant evidence for the association (TDT chi2 = 4.48, P = 0.017). We also detected a trend for linkage and association in the DRD5 polymorphism (TDT chi2 = 2. 38, P = 0.06). 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Similar findings were obtained in relation to MPH response as analysis of MPH responders alone gave rise to a more significant association than that of the group as a whole (TDT chi2 = 4.9, P = 0.013). t-Test and logistic regression TDT analyses of DRD4*7 transmission with respect to dimensional rating scales of hyperactivity and impulsivity showed an inverse relation suggesting that in this sample DRD4*7 is associated with a lower level of ADHD symptomatology. While this may be due to stratification along a dimension of severity such that severe cases belong to a more extreme group with other specific genetic and environmental causes, similar to the model for low cognitive ability, it is more likely the result of a chance selection bias in this sample.</abstract><cop>Basingstoke</cop><pub>Nature Publishing Group</pub><pmid>10889550</pmid><doi>10.1038/sj.mp.4000744</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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ispartof Molecular psychiatry, 2000-07, Vol.5 (4), p.396-404
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subjects Alleles
Attention Deficit Disorder with Hyperactivity - drug therapy
Attention Deficit Disorder with Hyperactivity - genetics
Attention deficit disorders. Hyperactivity
Attention deficit hyperactivity disorder
Biological and medical sciences
Child
Child clinical studies
Children
Cognitive ability
DNA nucleotidylexotransferase
Dopamine
Dopamine D4 receptors
Dopamine D5 receptors
Dopamine receptors
Dopamine Uptake Inhibitors - administration & dosage
Family Health
Genes
Genetic factors
Genetic Linkage
Humans
Hyperactivity
Impulsive behavior
Impulsivity
Logistic Models
Medical sciences
Methylphenidate
Methylphenidate - administration & dosage
Polymorphism, Genetic
Psychiatry
Psychology. Psychoanalysis. Psychiatry
Psychopathology. Psychiatry
Receptors, Dopamine D1 - genetics
Receptors, Dopamine D2 - genetics
Receptors, Dopamine D4
Receptors, Dopamine D5
Synapses
Treatment Outcome
Turkey
title Association and linkage of DRD4 and DRD5 with attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children
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