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	Kim CH, 200617146058
Citation	Kim C. H., Hahn M. K., Joung Y., Anderson S. L., Steele A. H., Mazei-Robinson M. S., Gizer I., Teicher M. H., Cohen B. M., Robertson D., Waldman I. D., Blakely R. D. and Kim K. S. (2006) "A polymorphism in the norepinephrine transporter gene alters promoter activity and is associated with attention-deficit hyperactivity disorder." Proc Natl Acad Sci U S A, 103(50): 19164-9.
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	94 patients and 60 controls
Predominant Ethnicity	USA
Population	USA
Age Group	Children/Adolescents

Detail Info

Summary	In this study, they report a previously uncharacterized and common A/T polymorphism at -3081 upstream of the transcription initiation site of the human norepinephrine transporter gene [solute carrier family 6, member 2 (SLC6A2)]. Using both homologous and heterologous promoter-reporter constructs, they found that the -3081(T) allele significantly decreases promoter function compared with the A allele. Interestingly, this T allele creates a new palindromic E2-box motif that interacts with Slug and Scratch, neural-expressed transcriptional repressors binding to the E2-box motif. They also found that both Slug and Scratch repress the SLC6A2 promoter activity only when it contains the T allele. Finally, they observed a significant association between the -3081(A/T) polymorphism and attention-deficit hyperactivity disorder (ADHD), suggesting that anomalous transcription factor-based repression of SLC6A2 may increase risk for the development of attention deficit hyperactivity disorder and other neuropsychiatric diseases.
Total Sample	94 patients who met Diagnostic and Statistical Manual of Mental Disorders, 4th Ed. (DSM-IV) criteria for ADHD and 60 unaffected controls
Sample Collection	African-USAn; European-USAn, Hispanic, or Asian ethnicity
Diagnosis Description	At the Vanderbilt site, the Kiddie-SADS-Present and Lifetime Version was used to determine whether DSM-IV criteria for ADHD were met, whereas at the Emory site, a DSM-IV symptom questionnaire was used to rule out ADHD in the nondisordered controls. At the McLean site, ADHD subjects between the ages of 6 and 17 years were diagnosed when they met DSM-IV criteria.
Technique	The SNP was genotyped using PCR restriction fragment length polymorphism (RFLP) analysis. For analysis of genomic DNA samples, a 1,360-bp region containing nucleotides -4000 to -3018 of SLC6A2 was amplified by PCR with primers NET24S (5'- GAATTCAGGGCAGGTCAGCTG-3') and NET38A (5'- GAGACAGCAAAGGGAAGGAAACCA-3'). PCR was carried out under the condition used in their previous study. The resulting PCR products then were purified by 7% polyacrylamide gel electrophoresis and directly sequenced.
Analysis Method	Crosstabs and logistic regression analyses with two-tailed P-values were conducted by using SPSS for Windows (SPSS, Chicago, IL) version 14 and were used to compare allele and genotype frequencies between ADHD cases and nondisordered controls.
Result Description	They observed a significant association between the -3081(A/T) polymorphism and attention-deficit hyperactivity disorder (ADHD), suggesting that anomalous transcription factor-based repression of SLC6A2 may increase risk for the development of attention deficit hyperactivity disorder and other neuropsychiatric diseases.

Other variant reported by this study (count: 1)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
SLC6A2 promoter -3081A/T			frequency of -3081(T) allele, P-value=0.008, OR=2.00, X^...... frequency of -3081(T) allele, P-value=0.008, OR=2.00, X²=7.07; logistic regression results for the linear trend contrasting the number of T alleles: P-value=0.011, R²=0.06, X²=6.49 More...	a significant association was observed	Significant

Genes reported by this study (count: 1)