Objective: To investigate association of the 48 bp variable number of tandem repeat (VNTR) polymorphism in the D4 receptor gene (DRD4) exon 3 and 40 bp VNTR polymorphism in the dopamine transporter gene (DAT1) 3' untranslated region with attention deficit hyperactivity disorder (ADHD) in Han Chinese children.
Methods: The study samples were comprised of 340 ADHD children, 226 unrelated controls and 202 integrated ADHD trios (included proband and biological parents). The polymorphisms consisted of 48 bp VNTR in exon 3 of DRD4, and 40 bp VNTR in the 3' untranslated region of DAT1. Associations of polymorphisms with ADHD and its subtypes were examined by: (i) comparing cases and controls; and (ii) using family-based association study in an extension of exact transmission-disequilibrium test (ETDT) and haplotype-based haplotype relative risk (HHRR).
Results: The repeat numbers at the DRD4 48 bp locus ranged from 2-6 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, the repeat numbers at the 40 bp locus ranged from 6-7 repeats and 9-11 repeats. The 10-repeat allele was the most frequent (90.7%). The long-repeat alleles of DRD4 (ranging from 4-6 repeats) and DAT1 (ranging from 11-12 repeats), were present more frequently in ADHD probands than in controls. Our primary analyses failed to replicate the associations between ADHD and 7-repeat allele of DRD4 and the 10-repeat allele of DAT1.
Conclusion: The long-repeat alleles of DRD4 (after a stratification by gender) and DAT1 may increase the risk for ADHD in Han Chinese children.