Family-based and case-control association studies of DRD4 and DAT1 polymorphisms in Chinese attention deficit hyperactivity disorder patients suggest long repeats contribute to genetic risk for the disorder.
Molecular genetic studies of attention deficit hyperactivity disorder (ADHD) have implicated the variable number of tandem repeat (VNTR) polymorphisms of two candidate genes, the dopamine D4 receptor (DRD4) and the dopamine transporter (DAT1). We sought to determine if these genes were relevant to the etiology of ADHD in China by using both family-based (N = 202 nuclear ADHD families) and case-control (N = 340 ADHD cases, and 226 controls) association study designs. Diagnoses and subtypes were ascertained according to Clinical Diagnostic Interview Scales (CDIS) using DSM-IV criteria. The repeat numbers at the DRD4 VNTR ranged from 2 to 6 repeats in the Han Chinese controls, with the most common being the 4-repeat (77%) and 2-repeat (19.4%) alleles. Neither the 7-repeat allele nor longer repeats were found. For the DAT1 VNTR, the repeat numbers ranged from 6 to 7 repeats and 9 to 11 repeats. The 10-repeat allele was the most frequent (90.7%). The long-repeat alleles of DRD4 (ranging from 4 to 6 repeats) and DAT1 (ranging from 11 to 12 repeats), were present more frequently in ADHD probands than controls (P < 0.05), although there was no significant allelic association when the alleles were analyzed separately from each other and there findings were not supported by within family tests of association. An exploratory stratification by gender suggests that long-repeat alleles of DRD4 and DAT1 may increase the risk for ADHD in Han Chinese children.
Qian
Qiujin
Q
Institute of Mental Health, Peking University, Beijing 100-083, China.
Wang
Yufeng
Y
Zhou
Rulun
R
Yang
Li
L
Faraone
Stephen V
SV
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002681:China / Q000453:epidemiology; D050483:Dopamine Plasma Membrane Transport Proteins; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics; D018598:Minisatellite Repeats; D017720:Molecular Epidemiology; D009419:Nerve Tissue Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D017448:Receptors, Dopamine D2 / Q000235:genetics; D050638:Receptors, Dopamine D4; D012306:Risk; D012737:Sex Factors
C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4