| Summary |
The aim of the study was to test whether dopamine transporter gene (DAT1) and dopamine receptor D4 gene (DRD4) polymorphisms are in linkage disequilibrium with ADHD in Korean children, using a family-based association study. One hundred and twenty-six trios were studied and 87% of probands were boys. ADHD not otherwise specified (NOS) was the most common subtype and comorbidity rates were low. Descriptive analysis and the TDT test were the primary analyses. In exploratory analyses, logistic regression and QTDT were performed. The 10-repeat allele and 4-repeat allele were the most frequent for DAT1 and DRD4. TDT test for DAT1 and DRD4 did not show preferential transmission. Based on logistic regression and QTDT, the 5-repeat allele of DRD4 may confer protection for hyperactive-impulsivity symptom severity compared to the 4-repeat allele. |
| Total Sample |
The study subjects consisted of 136 families: 10 families were dropped from the final analysis due to exclusion criteria including low IQ, the presence of tics, and the failure to meet the K-SADS-PL-K threshold diagnostic criteria for ADHD. Among the final 126 families, 19 families did not have complete genotyping because one or two family members did not complete blood collection. Of the probands, 87% were boys. Mean age of the probandswas 8.3 years (S.D.=1.8) and the mean IQ was 104 (S.D.=16). |
| Sample Collection |
Consecutive subjects consenting to participate in a family-based association study for ADHD and their biological parents were studied between September 2000 and August 2002 at four, university-based, South Korean child psychiatry outpatient clinics (Hallym University, Yonsei University, Seoul National University and Gyeongsang National University). |
| Diagnosis Description |
The children included in the study met DSM-IV diagnostic criteria for ADHD on the Diagnostic Interview Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime- Korean Version (K-SADS-PL-K.) Good to excellent validity and reliability of K-SADS-PL-K in ADHD and other disruptive behavioral disorders were reported in Korean children. The DSM-IV diagnoses of ADHD subtypes included inattentive type 28%, hyperactive-impulsive type 8%, combined type 29% and not otherwise specified 36%. |
| Technique |
DNA was extracted from whole blood using a standard DNA isolation procedure. For each locus, PCR was carried out in a 10 ul volume containing 50 ng of genomic template, 0.5 uM of each primer, one of which was 5' fluorescently labeled, 200uM of each dNTP, 1X PCR buffer, 1.5 mM MgCl2, and 0.3 units of DyNAzymeTM EXT DNA polymerase (Finnzymes Oy, Espoo, Finland), with 0.5M GC-melt (Clontech, Palo Alto, CA, USA). Primer sequences were as follows: DAT1, 5'-NEDTGTGGTGTAGGGAACGGCCTGAG- 3' and 5'-CTTCCTGGAGGTCACGGCTCAAGG- 3'; For DRD4, 5'-FAM-GCGACTACGTGGTCTACTCG- 3' and 5'-GGTCTGCGGTGGAGTCTG- 3'. For more detailed information, please refer to the original publication. |
| Analysis Method |
Sib-tdt test was used for TDT (ASPEX version 2.2). To test for an interaction between DRD4 and DAT1, they created a 'pseudohaplotype' of these two genes to look for preferential transmission of a particular combination of DAT1 and DRD4 alleles. TDTPHASE was used for this analysis. In exploratory analyses, they analyzed quantitative measures of ADHD. ANOVA were performed to explore the mean differences of the quantitative measures of inattention and hyperactive-impulsivity amongst the most common genotypes of DAT1 and DRD4. The associations between those common genotypes of DAT1 and DRD4 and the quantitative measures were tested using logistic regression. |
| Result Description |
The 10-repeat allele and 4-repeat allele were the most frequent for DAT1 and DRD4. TDT test for DAT1 and DRD4 did not show preferential transmission. Based on logistic regression and QTDT, the 5-repeat allele of DRD4 may confer protection for hyperactive-impulsivity symptom severity compared to the 4-repeat allele. |
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