Association between the dopamine transporter gene and the inattentive subtype of attention deficit hyperactivity disorder in Taiwan.
Attention deficit hyperactivity disorder (ADHD) is a common heritable childhood psychiatric disorder. Since methylphenidate, one of the main drugs used to treat ADHD, targets the dopamine transporter, this study examined the linkage disequilibrium (LD) structure of the dopamine transporter gene (DAT1) and investigated whether the DAT1 gene was associated with ADHD. This Chinese family-based association sample consisted of 273 DSM-IV diagnosed ADHD probands and their family members (n=906). We screened 15 polymorphisms across the DAT1 gene, including 14 single nucleotide polymorphism (SNP) markers and the variable number of tandem repeat (VNTR) polymorphism in 3'-untranslated region (3'UTR). Calculations of pairwise LD revealed three main haplotype blocks (HBs): HB1 (intron 2 through intron 6), HB2 (intron 8 through intron 11), and HB3 (3'UTR). Family-Based Association Tests showed that no allele was significantly more transmitted than expected to the ADHD children for these 15 markers. Haplotype-Based Association Tests showed that a haplotype rs27048 (C)/rs429699 (T) was significantly associated with the inattentive subtype (P=0.008). In quantitative analyses, this haplotype also demonstrated significant association with the inattention severity (P=0.012). Our finding of the haplotype rs27048 (C)/rs429699 (T) as a novel genetic marker in the inattentive ADHD subtype suggests that variation in the DAT1 gene may primarily affect the inattentive subtype of ADHD.
Shang
Chi-Yung
CY
Department of Psychiatry, National Taiwan University Hospital, Taipei, Taiwan.
Gau
Susan Shur-Fen
SS
Liu
Chih-Min
CM
Hwu
Hai-Gwo
HG
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000175:diagnosis* / Q000235:genetics*; D002648:Child; D018450:Disease Progression; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005820:Genetic Testing; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D013624:Taiwan
D050483:Dopamine Plasma Membrane Transport Proteins; D005819:Genetic Markers