Study Report
Basic Info
Reference |
Eisenberg J, 199910490706
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Citation |
Eisenberg J., Mei-Tal G., Steinberg A., Tartakovsky E., Zohar A., Gritsenko I., Nemanov L. and Ebstein R. P. (1999) "Haplotype relative risk study of catechol-O-methyltransferase (COMT) and attention deficit hyperactivity disorder (ADHD): association of the high-enzyme activity Val allele with ADHD impulsive-hyperactive phenotype." Am J Med Genet, 88(5): 497-502.
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Study Design |
family-based |
Study Type |
Candidate-gene association study |
Sample Size |
48 ADHD probands and their parents |
Predominant Ethnicity |
Ashkenazi Jews, non-Ashkenazi Jews |
Population |
Israel |
Gender |
40 males and eight females |
Age Group |
Children/Adolescents
:
5-17 years (average age=9.4, SD=2.5)
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Detail Info
Summary |
In the current investigation, a catechol-O-methyltransferase (COMT) polymorphism that codes for a high versus low enzyme COMT activity was examined using family-based methods for a role in ADHD. Using a haplotype relative risk design and a parent-to-proband allele transmission test with 48 ADHD triads, they found an association between COMT and illness. In particular, the impulsive-hyperactive type of ADHD (excluding inattention) ascertained by Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria, by the Conners Teaching Rating Hyperactivity scale as well as by the Continuous Performance Test False Alarm scale were associated with the high enzyme activity COMT val allele. Similar results were obtained if genotype frequencies were compared. It should be noted that the association between the high-enzyme activity COMT val allele that increases CNS dopamine (and norepinephrine) clearance is consistent with the use of methylphenidate, an agent that increases dopamine (and norepinephrine) turnover, in the treatment of this disorder. These provisional findings suggest that newly developed COMT inhibitors such as tolcapone, applied in Parkinson's disease, might in due time be considered in the treatment of ADHD. |
Total Sample |
The probands consisted of 40 males and eight females from 46 families. The average age was 9.4 years, SD 2.5 (range 5-17 years). The percentage of probands with ADHD combined type was 57%, inattentive 33%, impulsive 10%. Among probands participating in the study 39% met criteria for comorbid oppositional defiance disorder or conduct disorder. Transient tics were displayed in 18% of the probands. |
Sample Collection |
ADHD subjects and their families were recruited for participation in this study from a child psychiatry unit in a community mental health center and from several child neurology clinics in the Jerusalem municipal area. |
Diagnosis Description |
The criteria for eligibility included Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria according to the K-SAD-PL (Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version) [Shanee, 1966]. |
Technique |
DNA was extracted from frozen blood using a Qiamp kit (Qiagen, Germany). Each individual was typed for high and low COMT activity (val/met polymorphism) by amplification of a 169 base pair fragment by using PCR. |
Analysis Method |
family-based HRR design by using SPSS for Windows |
Result Description |
They found an association between COMT and illness (X2 = 4.72, p = 0.03, df = 1). In particular, the impulsive-hyperactive type of ADHD (excluding inattention) ascertained by Diagnostic and Statistical Manual of Mental Disorders (DSM IV) criteria (X2 = 8.34, p = 0.004, df = 1), by the Conners Teaching Rating Hyperactivity scale (Pearson X2 = 5.32, p = 0.02, df = 1) as well as by the Continuous Performance Test False Alarm scale (X2 = 2.78, p = 0.096, df = 1) were associated with the high enzyme activity COMT val allele. Similar results were obtained if genotype frequencies were compared. |
SNPs reported by this study (count: 1)
SNP |
Allele Change |
Risk Allele |
Statistical Values |
Author Comments |
Result of Statistical Analysis |
rs4680 |
Val/Met |
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HRR P-value=0.03, X2=4.72, df=1 for the transmission of high enzyme activity COMT val allele to ADHD probands; HRR P-value=0.004, X2=8.34, df=1 for the transmission of high enzyme activity COMT val allele to impulsive or combined-type probands; HRR P-value=1.0, X2=0.000, df=1 between COMT allele frequency and inattentive type probands |
The results of HRR analysis showed significant association b......
The results of HRR analysis showed significant association between COMT val allele and ADHD and impulsive or combined-type ADHD.
More...
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Significant
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Genes reported by this study (count: 1)
Gene |
Statistical Values/Author Comments |
Result of Statistical Analysis |
COMT |
No significant association was observed between COMT genotyp......
No significant association was observed between COMT genotype and ADHD although there was an excess of the Val/Val genotype: HRR P-value=0.05, X2=5.98, df=2; there was a significant association of the COMT polymorphism and ADHD
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Significant
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