No evidence for the association of DRD4 with ADHD in a Taiwanese population within-family study

Xu, Xiaohui; Chen, Chih‐Ken; Huang, Yu-Shu; Wu, Yu‐Yu; Asherson, Philip

doi:10.1186/1471-2350-6-31

Cited by 32 publications

(25 citation statements)

References 47 publications

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“…Many association studies between DRD4 and ADHD have been performed, although results are often controversial. In this regard, although our data in the single-marker analysis are in agreement with previous reports showing no association between ADHD and the 48bpVNTR polymorphism [Roman et al, 2001;Todd et al, 2001;Bakker et al, 2005;Brookes et al, 2005;Carrasco et al, 2006;Johansson et al, 2008;Sonuga-Barke et al, 2008], they are contrary to others having reported on association between the 7R allele and the disorder Faraone et al, 2001;Maher et al, 2002;Wohl et al, 2005;Brookes et al, 2006;Li et al, 2006;Gizer et al, 2008Gizer et al, , 2009Biederman et al, 2009;Langley et al, 2009;Nikolaidis and Gray, 2010]. Likewise, our results for the DRD4 dup120bp polymorphism are in line with most of the literature, including a recent meta-analysis [Barr et al, 2001;Todd et al, 2001;Mill et al, 2003;Kirley et al, 2004;Brookes et al, 2005;Bhaduri et al, 2006;Gizer et al, 2009], but not with findings from the first two association analyses of this variation [McCracken et al, 2000].…”

Section: Discussionsupporting

confidence: 93%

“…In this regard, the 240 bp allele (long or L allele) showed enhanced binding capacity for the Sp1 transcription factor in a mobility shift assay and exhibited lower transcriptional activity than the 120 bp allele (short or S allele) in transfected cell lines [D'Souza et al, 2004;Ronai et al, 2004;Kereszturi et al, 2007]. Several studies have tested association between the DRD4 dup120bp polymorphism and ADHD but results are also controversial, showing no association [Barr et al, 2001;Todd et al, 2001;Brookes et al, 2005;Bhaduri et al, 2006;Gizer et al, 2009] or identifying either the L or S alleles as risk factors for ADHD [McCracken et al, 2000;Kustanovich et al, 2004;Kereszturi et al, 2007]. Accordingly, a recent meta-analysis performed by Gizer et al [2009] found no association between childhood ADHD and either allele.…”

Section: Introductionmentioning

confidence: 99%

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Exploring DRD4 and its interaction with SLC6A3 as possible risk factors for adult ADHD: A meta‐analysis in four European populations

Sánchez-Mora

Ribasés

Casas

et al. 2011

American J of Med Genetics Pt B

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Attention-deficit hyperactivity disorder (ADHD) is a common behavioral disorder affecting about 4-8% of children. ADHD persists into adulthood in around 65% of cases, either as the full condition or in partial remission with persistence of symptoms. Pharmacological, animal and molecular genetic studies support a role for genes of the dopaminergic system in ADHD due to its essential role in motor control, cognition, emotion, and reward. Based on these data, we analyzed two functional polymorphisms within the DRD4 gene (120 bp duplication in the promoter and 48 bp VNTR in exon 3) in a clinical sample of 1,608 adult ADHD patients and 2,352 controls of Caucasian origin from four European countries that had been recruited in the context of the International Multicentre persistent ADHD CollaboraTion (IMpACT). Single-marker analysis of the two polymorphisms did not reveal association with ADHD. In contrast, multiplemarker meta-analysis showed a nominal association (P ¼ 0.02) of the L-4R haplotype (dup120bp-48bpVNTR) with adulthood ADHD, especially with the combined clinical subtype. Since we previously described association between adulthood ADHD and the dopamine transporter SLC6A3 9R-6R haplotype (3 0 UTR VNTR-intron 8 VNTR) in the same dataset, we further tested for gene Â gene interaction between DRD4 and SLC6A3. However, we detected no epistatic effects but our results rather suggest additive effects of the DRD4 risk haplotype and the SLC6A3 gene.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Exploring DRD4 and its interaction with SLC6A3 as possible risk factors for adult ADHD: A meta‐analysis in four European populations

Sánchez-Mora

Ribasés

Casas

et al. 2011

American J of Med Genetics Pt B

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“…8,28 Standard PCR protocols were used for all VNTR markers and amplified products visualised on 2% agarose under UV light, as previously described. [31][32][33] SNP selection We adopted a 'biological systems' approach by nominating 46 genes that were likely to exert an effect through regulation of dopamine, serotonin and norepinephrine neurotransmission, as well as six circadian rhythm genes. Selected genes fell into the following functional groups: dopamine receptors, serotonin receptors, norepinephrine receptors, neurotransmitter metabolic and catabolic enzymes, neuronal transporters, synaptic vesicle associated proteins, fatty acid desaturase enzymes and circadian rhythm genes (listed in Table 1).…”

Section: Clinical Proceduresmentioning

confidence: 99%

The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes

et al. 2006

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Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, starting in early childhood and persisting into adulthood in the majority of cases. Family and twin studies have demonstrated the importance of genetic factors and candidate gene association studies have identified several loci that exert small but significant effects on ADHD. To provide further clarification of reported associations and identify novel associated genes, we examined 1038 single-nucleotide polymorphisms (SNPs) spanning 51 candidate genes involved in the regulation of neurotransmitter pathways, particularly dopamine, norepinephrine and serotonin pathways, in addition to circadian rhythm genes. Analysis used within family tests of association in a sample of 776 DSM-IV ADHD combined type cases ascertained for the International Multi-centre ADHD Gene project. We found nominal significance with one or more SNPs in 18 genes, including the two most replicated findings in the literature: DRD4 and DAT1. Gene-wide tests, adjusted for the number of SNPs analysed in each gene, identified associations with TPH2, ARRB2, SYP, DAT1, ADRB2, HES1, MAOA and PNMT. Further studies will be needed to confirm or refute the observed associations and their generalisability to other samples. Molecular Psychiatry (2006) 11, 934-953.

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“…After the meta-analysis, three studies of association between ADHD and the exon 3 polymorphism of the DRD4 gene have been performed in Chinese populations which yielded different findings. Leung and colleagues found that the 2-repeat allele was associated with ADHD in a population of Chinese children in Hong Kong [Leung et al, 2005] [Brookes et al, 2005]. More studies involving Chinese and other ethnicities are certainly needed for replication of these results before a firm conclusion can be made about the association between ADHD and exon 3 polymorphisms of the DRD4 gene.…”

mentioning

confidence: 86%

Exon 3 polymorphisms of dopamine D4 receptor (DRD4) gene and attention deficit hyperactivity disorder in Chinese children

Cheuk

Wong

2006

American J of Med Genetics Pt B

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Dopamine D4 receptor (DRD4) gene is implicated in the pathogenesis of attention deficit hyperactivity disorder (ADHD). The 7-repeat allele of the variable-number-of-tandem-repeat (VNTR) polymorphism in exon 3 has been reported to be associated with ADHD. However, studies in Chinese populations have yielded conflicting results. We therefore perform another study to investigate the association between ADHD and DRD4 gene polymorphism in Chinese children in Hong Kong. In this prospective family-based and case-control study during January-June 2004, we recruited consecutive Chinese children diagnosed with ADHD by DSM-IV and sex-matched controls admitted for acute upper respiratory infection, excluding those with perinatal brain insults, mental retardation, or neurological deficits. VNTR polymorphisms of the DRD4 gene were determined by standard PCR followed by agarose gel electrophoresis. Sixty-four ADHD cases (52 boys, 12 girls), their family members, and 64 normal controls were recruited. The 4-repeat allele (84.4%) and the 4/4-repeat genotype (70.3%) were the most prevalent. Both family-based and case-control analyses showed no association between ADHD and DRD4 gene polymorphisms (transmission dysequilibrium test (TDT): P = 0.91 and P = 0.33 for the 7-repeat and 4-repeat alleles, respectively; OR for the 7-repeat allele = 2.01 (95% CI 0.07-60.4, P = 0.66), OR for the 4-repeat allele = 1.51 (95% CI 0.80-2.85, P = 0.2)). However, the longer repeat alleles had a positive trend association with ADHD (P = 0.01) in the case-control analysis. We concluded that ADHD is not associated with a particular VNTR polymorphism of the DRD4 gene. Further studies are needed to clarify the role of repeat length of the VNTR region of the DRD4 gene in the pathogenesis of ADHD.

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No evidence for the association of DRD4 with ADHD in a Taiwanese population within-family study

Cited by 32 publications

References 47 publications

Exploring DRD4 and its interaction with SLC6A3 as possible risk factors for adult ADHD: A meta‐analysis in four European populations

Exploring DRD4 and its interaction with SLC6A3 as possible risk factors for adult ADHD: A meta‐analysis in four European populations

The analysis of 51 genes in DSM-IV combined type attention deficit hyperactivity disorder: association signals in DRD4, DAT1 and 16 other genes

Exon 3 polymorphisms of dopamine D4 receptor (DRD4) gene and attention deficit hyperactivity disorder in Chinese children

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