| Summary |
A sample of 81 Brazilian ADHD children and adolescents and their parents were screened for these DRD4 and DAT1 VNTRs. An excess of the DRD4 7-repeat allele was observed when both ADHD probands and their parents were compared with an ethnically matched control sample. However, haplotype relative risk (HRR) analysis showed no preferential transmission of the DRD4 7-repeat allele. No evidence of association with the DAT1 polymorphism was detected by both approaches. Nevertheless, an interaction effect of both genes on ADHD hyperactive/ impulsive dimension was observed. These results add to the group of studies that together suggest a small effect of these genes in the susceptibility to ADHD. |
| Total Sample |
Eighty-one children and adolescents and 130 parents were assessed from 77 families. Forty-nine families consisted of mother, father, and one affected child, 4 families consisted of mother, father, and two affected children, while 24 families consisted of mother or father and the affected child. Most of them were male (86.4%) from European descent (86.4%). A sample composed of about 100 subjects ascertained at a paternity testing service and already typed for DRD4 [Roman et al., 1999] and DAT1 [Bau et al., 2001] VNTRs was used for comparison of allele frequencies with ADHD probands or their parents. |
| Sample Collection |
Patients were drawn from the ADHD outpatient clinic at the Child and Adolescent Psychiatric Division of Hospital de Clinicas de Porto Alegre (HCPA). |
| Diagnosis Description |
In addition to the extensive diagnostic procedure, parents completed the Child Behavior Checklist (CBCL), Parent Report Form [Achenbach, 1991], a behavior symptom check list that reports children's behavioral problems and social competencies; its Attention Problems scale has a high discriminating power for the clinical diagnoses of ADHD [Chen et al., 1994]. Also, for probands who were attending school, teachers completed the Attention Problems scale of the CBCL-Teacher Report Form (TRF) [Achenbach, 1991], which includes items related to ADHD in the classroom. The parents were evaluated for past (childhood) or present diagnosis of ADHD by a child psychiatrist. This evaluation was performed with the ADHD module from the K-SADS-E, modified to assess DSM-IV criteria. |
| Technique |
High-molecular-weight genomic DNA was extracted from whole blood by a salting-out procedure [Miller et al., 1988]. The DRD4 region containing the 48 bp repeat was amplified by the polymerase chain reaction (PCR) as described by Roman et al. [1999]. PCR amplification of the 40 bp VNTR site at DAT1 gene was performed according to Sano et al. [1993]. The DRD4 and DAT1 PCR products were electrophoresed respectively on 3.5% and 2.5% agarose gels, stained with ethidium bromide. Fifty bp and 100 bp ladders were used to score the various repeat alleles. |
| Analysis Method |
Allele frequencies at the individual loci were estimated by counting. Heterogeneity of allele frequencies among ADHD probands, their parents, and the control sample was tested by the chi-square procedure for small numbers described by Roff and Bentzen [1989]; The chi-square partitioning was performed with the PEPI, version 2. The haplotype relative risk statistics was used. Families with two affected children were included as two independent trios in the HRR analyses. The interaction effect of both genes on ADHD inattentive and hyperactive/ impulsive scores was investigated by a two-way analysis of variance (ANOVA). A significance level of 5% was accepted in these comparisons. All statistical tests were carried out using SPSS, version 8.0 for Windows. |
| Result Description |
An excess of the DRD4 7-repeat allele was observed when both ADHD probands and their parents were compared with an ethnically matched control sample (chi-square=11.55, P=0.03; chi-square=12.17, P=0.03, respectively). However, haplotype relative risk (HRR) analysis showed no preferential transmission of the DRD4 7-repeat allele. No evidence of association with the DAT1 polymorphism was detected by both approaches. Nevertheless, an interaction effect of both genes on ADHD hyperactive/ impulsive dimension was observed (F=4.68; P=0.03). |
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