Family-based association study of DAT1 and DRD4 polymorphism in Korean children with ADHD

• Published in: Neuroscience letters 2005-12, Vol.390 (3), p.176-181
• Main Authors: Kim, Young Shin, Leventhal, Bennett L., Kim, Soo-Jeong, Kim, Boong-Nyun, Cheon, Keun-Ah, Yoo, Hee-Jeong, Kim, Se-Joo, Badner, Judith, Cook, Edwin H.
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Attention Deficit and Disruptive Behavior Disorders - genetics; Biological and medical sciences; Child; DAT1; Dopamine Plasma Membrane Transport Proteins - genetics; DRD4 5-repeat allele; Family Health; Female; Fundamental and applied biological sciences. Psychology; Gene Frequency; Genetic Predisposition to Disease; Humans; Korea; Korean; Linkage Disequilibrium; Logistic Models; Male; Polymorphism, Genetic; Receptors, Dopamine D4 - genetics; TDT; Vertebrates: nervous system and sense organs
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2005.08.025

Although the etiology of Attention Deficit/Hyperactivity Disorder (ADHD) is not well understood, evidence from the family and twin studies suggest that ADHD is familial and highly heritable. 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 (mean age = 8.2 years, mean IQ = 104). 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. The negative TDT finding between DAT1 and DRD4 VNTR polymorphisms and ADHD should be interpreted with caution; partly due to lack of power caused by low heterozygosity in the study population. Future studies are necessary to test the hypothesis generated in this study that the 5-repeat allele of DRD4 is protective for hyperactive-impulsivity symptom severity compared to the 4-repeat allele.