Study Report
Basic Info
Reference |
Genro JP, 200717044101
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Citation |
Genro J. P., Zeni C., Polanczyk G. V., Roman T., Rohde L. A. and Hutz M. H. (2007) "A promoter polymorphism (-839 C > T) at the dopamine transporter gene is associated with attention deficit/hyperactivity disorder in Brazilian children." Am J Med Genet B Neuropsychiatr Genet, 144B(2): 215-9.
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Study Design |
family-based |
Study Type |
Candidate-gene association study |
Sample Size |
243 families |
Predominant Ethnicity |
Caucasian |
Population |
Brazil |
Gender |
82.6% of patients were males |
Age Group |
Children/Adolescents
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mean age 10.3 years (SD=3.1)
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Detail Info
Summary |
In this study, they tested DAT 3'-UTR VNTR polymorphism and an additional promoter polymorphism -839 C>T (Rs: 2652511) using familybased association analyses in a sample of 243 Brazilian ADHD children and adolescents and their parents. No significant linkage disequilibrium between the two polymorphisms was detected in this sample (D'=0.56; P-value=0.22). No evidence of association with the VNTR polymorphism was found. A significant association (P-value=0.03) for biased transmission of the C allele at the -839 C>T polymorphism to ADHD children in the total sample was observed, which was strengthened when the analyses were restricted to the ADHD combined type (P-value=0.004). The results suggest a role for the promoter region of DAT1 gene in ADHD susceptibility in this Brazilian sample. |
Total Sample |
The sample included 243 families comprising 186 parent proband trios and 57 parent-child duos. The first 81 families included in this sample have been previously described by Roman et al. [2001]. Most of them presented the combined type (65.6%), and oppositional defiant disorder was the most common comorbid condition (47%). |
Sample Collection |
Samples were recruited from the Child and Adolescent Psychiatric Division of the Hospital de Clinicas de Porto Alegre (HCPA). The ADHD patients were predominantly from European descent (92.1%). |
Diagnosis Description |
A consensus diagnosis of ADHD based on DSM-IV criteria was achieved through a three-stage process, described in detail previously [Roman et al., 2001; Rohde, 2002]. |
Technique |
DNA was extracted from whole blood lymphocytes by a salting out procedure as described by Lahiri and Nurnberger [1991]. The 3'-VNTR polymorphism and promoter polymorphism -839 C>T was amplified using the polymerase chain reaction (PCR), with protocols previously described by Roman et al. [2001] and Rubie et al. [2001], respectively. |
Analysis Method |
Allele frequencies were estimated by counting. Linkage disequilibrium was estimated using the ARLEQUIN software (version 2.000). Dmax and D' values were calculated as described by Lewontin [1988]. Individual genotype data were analyzed for the complete sample using the statistical package TRANSMIT. Haplotype-based associations were also tested using the TRANSMIT program. The association between genetic markers and disease was also analyzed by the transmission disequilibrium test (TDT) and the Fbat statistics using the FBAT software. A significance level of 5% was accepted in these comparisons. |
Result Description |
Six alleles were detected at the DAT1 3'-VNTR, and the most common alleles were the 10R and 9R. At the -839 C>T site, allele frequencies in both markers did not show any significant deviation from those expected according to Hardy-Weinberg equilibrium. A significant association for biased transmission of the C allele at the -839 C>T polymorphism to ADHD children in the total sample was observed, which was strengthened when the analyses were restricted to the combined type only. Biased transmission of the C allele for the combined subtype was also observed in the TDT analyses, using only trios with heterozygous parents. Either on the total sample or on the combined one, no allele was significantly more transmitted than expected for the 3'-VNTR polymorphism in the families with ADHD children. No significant linkage disequilibrium between the 3'-VNTR and the -839 C>T polymorphism was observed in this sample. No association with haplotypes was observed as expected due to non-significant LD. |
SNPs reported by this study (count: 1)
SNP |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result of Statistical Analysis |
rs2652511 |
C/T |
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Allelic test P-value=0.03 in the total sample, P-value=0.004 in combined type sample, TDT analysis P-value=0.13 in the total sample, P-value=0.03 in combined type sample |
A significant association for biased transmission of the C a......
A significant association for biased transmission of the C allele at the -839 C>T polymorphism to ADHD children in the total sample was observed, which was strengthened when the analyses were restricted to the combined type only. Biased transmission of the C allele for the combined subtype was also observed in the TDT analyses,
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Significant
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Other variant reported by this study (count: 1)
Variant Name |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result of Statistical Analysis |
SLC6A3 3'-UTR VNTR |
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Allelic test P-value=0.78 in the total sample, P-value=0.78 ......
Allelic test P-value=0.78 in the total sample, P-value=0.78 in combined type sample; TDT analysis P-value=0.63 in the total sample, P-value=0.42 in combined type sample
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Either on the total sample or on the combined one, no allele was significantly more transmitted than expected for the 3'-VNTR polymorphism in the families with ADHD children. |
Non-significant
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Genes reported by this study (count: 1)
Gene |
Statistical Values/Author Comments |
Result of Statistical Analysis |
SLC6A3 |
Results in this study suggest a role for the promoter region......
Results in this study suggest a role for the promoter region of SLC6A3 gene in ADHD susceptibility in the Brazilian sample.
More...
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Significant
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