- Title
- Is there a role for rare variants in DRD4 gene in the susceptibility for ADHD Searching for an effect of allelic heterogeneity
- Creator
- Tovo-Rodrigues, Luciana; Rohde, Luis; Roman, Tatiana; Schmitz, Marcelo; Polanczyk, Guilherme; Zeni, Cristian; Marques, Francine; Contini, Veronica; Grevet, Eugenio; Belmonte-De-Abreu, Paulo; Bau, Claiton; Hutz, Mara
- Date
- 2012
- Type
- Text; Journal article
- Identifier
- http://researchonline.federation.edu.au/vital/access/HandleResolver/1959.17/74527
- Identifier
- vital:7300
- Identifier
- http://www.scopus.com/inward/record.url?eid=2-s2.0-84860210990&partnerID=40&md5=44d7099e1c6e6bb4f269e5d0453c850b
- Identifier
- ISSN:1359-4184
- Abstract
- Although several studies have demonstrated an association between the 7-repeat (7R) allele in the 48-bp variable number of tandem repeats (VNTRs) in the exon 3 at dopamine receptor D4 (DRD4) gene and attention-deficit/ hyperactivity disorder (ADHD), others failed to replicate this finding. In this study, a total of 786 individuals with ADHD were genotyped for DRD4 exon 3 VNTR. All 7R homozygous subjects were selected for VNTR re-sequencing. Subjects homozygous for the 4R allele were selected paired by age, ancestry and disorder subtypes in order to have a sample as homogeneous as possible with 7R/7R individuals. Using these criteria, 103 individuals (66 with ADHD and 37 control individuals) were further investigated. An excess of rare variants were observed in the 7R alleles of ADHD patient when compared with controls (P = 0.031). This difference was not observed in 4R allele. Furthermore, nucleotide changes that predict synonymous and non-synonymous substitutions were more common in the 7R sample (P = 0.008 for total substitutions and P = 0.043 for non-synonymous substitutions). In silico prediction of structural/functional alterations caused by these variants have also been observed. Our findings suggest that not only repeat length but also DNA sequence should be assessed to better understand the role of DRD4 exon 3 VNTR in ADHD genetic susceptibility.; C1
- Relation
- Molecular Psychiatry Vol. 17, no. 5 (May 2012), p. 520-526
- Rights
- © 2012 Macmillan Publishers Limited All rights reserved.
- Rights
- No open access
- Rights
- This metadata is freely available under a CCO license
- Subject
- ADHD; DRD4; Rare variants; SH3-binding sites; VNTR; Dopamine 4 receptor; Allele; Attention deficit disorder; Computer model; Controlled study; Disease predisposition; DNA sequence; Exon; Gene sequence; Genetic heterogeneity; Genetic susceptibility; Genetic variability; Genotype; Human; Human tissue; Major clinical study; Nucleic acid base substitution; Nucleotide sequence; Priority journal; Alleles; Amino Acid Sequence; Attention Deficit Disorder with Hyperactivity; Base Sequence; Child; Exons; Female; Genetic Predisposition to Disease; Genetic Variation; Humans; Male; Minisatellite Repeats; Molecular Sequence Data; Receptors, Dopamine D4; 11 Medical and Health Sciences; 06 Biological Sciences; 17 Psychology and Cognitive Sciences
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