ADHDgene Database

Hot Results

Quick Search

Keyword:
Type:

Large-scale studies

Data Summary

Published Variant
- SNP: 1391
- CNV: 398
- Others: 173
Published Gene: 359
Published Region: 128
Pathway by PBA: 8
Study: 361

Study Report

Basic Info

Reference	Gabriela ML, 200919146920
Citation	Gabriela M. L., John D. G., Magdalena B. V., Ariadna G. S., Francisco de L. P., Liz S. M., Lino P. C., Josefina R. G., Ernesto R. Z. and Carlos C. F. (2009) "Genetic interaction analysis for DRD4 and DAT1 genes in a group of Mexican ADHD patients." Neurosci Lett, 451(3): 257-60.
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	105 cases, 105 controls
Predominant Ethnicity	Mexican
Population	Mexico
Age Group	Children/Adolescents : aged 12-18 years

Detail Info

Summary	They conducted a case-control association study between ADHD and two polymorphisms (the 7 repeat (R) allele in exon 3 of the dopamine receptor D4 (DRD4) and the 10R allele located in the 3' untranslated region (UTR) of the dopamine transporter (DAT1)) in a group of adolescent inhabitants of the metropolitan area of Mexico City. In addition, they evaluated the interaction between these genes, the disorder and its associated psychiatric comorbidities. No positive association between ADHD and the 7R allele of DRD4 or the 10R allele of DAT1 was observed; however, compared to controls, patients with internalized comorbidities had a lesser frequency of genotypes with the 7R allele of DRD4 and the 10/10 genotype of DAT1. A logistic regression analysis showed that the simultaneous absence of the 10/10 DAT1 and 7/7 DRD4 genotypes predicts membership to the group of ADHD patients with internalized comorbidities (e.g. anxiety, depression). The results highlight the importance of cross-ethnic research and the possibility of a distinct genetic basis that underlies the type of comorbidities associated with ADHD. This result should be considered in terms of the study design, and further replication is necessary in an independent sample.
Total Sample	105 patients were divided into three categories: externalized (n=48), internalized (n=52), and no comorbidity (n=5). 105 controls were chosen that were age and sex matched with the case group. Eleven additional samples were randomly selected, sequenced and included to minimize the loss of information due to genotyping problems. In addition, it was possible to obtain blood samples from the parents of 30 probands, which were subsequently analyzed in a family association study.
Sample Collection	Individuals who met diagnostic criteria for ADHD were recruited from the Clinic for Adolescents at the INPRF (the National Psychiatric Institute 'Ramon de la Fuente' in Mexico City). The control group included participants from a epidemiological survey of mental health in adolescents developed by the INPRF.
Diagnosis Description	A three-stage process was used to establish the ADHD diagnosis. For detailed information of this process, please refer to the original publication. Participants were excluded if the expressed symptoms were better explained by the presence of another psychiatric disorder, specifically pervasive developmental disorder.
Technique	Blood samples from the patients were drawn by venopunction and DNA was extracted by a conventional phenol-chlorophorm method. For the control group, mouthwash samples were obtained and DNA was extracted using the Puregene DNA purification Kit (GENTRA). Amplification of the DRD4 exon 3 VNTR was performed using conditions reported in (Aguirre AJ, 2007) and primers described by (Lichter JB, 1993). The DAT1 3'-UTR VNTR was performed as reported by (Kang AM, 1999). Genotyping was determined through agarose gel electrophoresis. Bands were compared with standards of known molecular weight and/or with the group of samples previously sequenced. Gels were read in a blind fashion by two different evaluators. Almost all samples were genotyped at least twice; doubtful genotypes were excluded from the analysis.
Analysis Method	Hardy-Weinberg equilibrium (HWE) was tested with the HW subroutine of the genetic LINKAGE program. Allele and genotype frequencies were analyzed with X²-test. A logistic regression analysis was used to evaluate the independent and interactive effect of the simultaneous absence of the 10/10 genotype of DAT1 and 7/7 genotype of DRD4 in ADHD patients and associated comorbidities. These analyses were run with SPSS software (v. 11). Bonferroni correctionwas then carried out for positive results and the significance level was set at 0.025 (0.05/2, two polymorphic systems). Finally, the transmission disequilibrium test (TDT) was performed using the 1.7.3 version of the FBAT program.
Result Description	No significant differences were found for allele and genotype frequencies between groups of comparison. The family study did not show a preferential allelic transmission for either of the genes. When the ADHD group was analyzed in terms of other expressed comorbidities a small decrement of 7R allele of DRD4 and the 10R allele of DAT1 in addition to a tendency towards an increasing number of 4R alleles in patients with internalized comorbidities was observed. A logistic regression analysis showed that the simultaneous absence of the 10/10 genotype of DAT1 and 7/7 genotype of DRD4 predicts the presence of ADHD with internalized comorbidities.

Genes reported by this study (count: 2)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
SLC6A3	genotype analysis P-value=0.57, allelic analysis P-value=0.5...... genotype analysis P-value=0.57, allelic analysis P-value=0.55, TDT P-value=0.8. No significant differences between groups of comparison. More...	Non-significant
DRD4	genotype analysis P-value=0.19; allelic analysis P-value=0.1...... genotype analysis P-value=0.19; allelic analysis P-value=0.18 \| TDT P-value=0.59. No significant differences between groups of comparison. More...	Non-significant