Attention-deficit/hyperactivity disorder and dopamine receptor D4 (DRD4) exon 3 variable number of tandem repeats (VNTR) 2-repeat allele

Ann Hum Genet. 2024 Sep;88(5):382-391. doi: 10.1111/ahg.12560. Epub 2024 Apr 16.

Abstract

To investigate the association of attention-deficit/hyperactivity disorder (ADHD) with the 48-base pair (bp) variable number of tandem repeats (VNTR) in exon 3 of the dopamine receptor D4 (DRD4) gene, we genotyped 240 ADHD patients and their parents from Hong Kong. The 4R allele was most common, followed by 2R. We examined association between the 2R allele (relative to 4R) and ADHD by Transmission Disequilibrium Test (TDT). The odds ratio (OR) (95% confidence interval) was 0.90 (0.64-1.3). The p-value was 0.6. Examining subgroups revealed nominally significant association of 2R with inattentive ADHD: OR = 0.33 (0.12-0.92) and p = 0.03. Because our study used TDT analysis, we meta-analyzed the association of 2R with ADHD in Asians (1329 patient alleles), revealing results similar to ours: OR = 0.97 (0.80-1.2) and p = 0.8. To examine the association of 2R with inattentive ADHD, we meta-analyzed all studies (regardless of analysis type or ethnicity, in order to increase statistical power): 702 patient alleles, 1420 control alleles, OR = 0.81 (0.57-1.1) and p = 0.2. Overall, there is no evidence of association between ADHD and the 2R allele, but the suggestive association with the inattentive type warrants further investigation.

Keywords: ADHD; dopamine; dopamine receptors; genetics; meta‐analysis; minisatellite repeats.

Publication types

  • Meta-Analysis

MeSH terms

  • Adolescent
  • Alleles*
  • Attention Deficit Disorder with Hyperactivity* / genetics
  • Child
  • Exons*
  • Female
  • Genetic Predisposition to Disease
  • Genotype
  • Hong Kong
  • Humans
  • Linkage Disequilibrium
  • Male
  • Minisatellite Repeats*
  • Receptors, Dopamine D4* / genetics

Substances

  • Receptors, Dopamine D4
  • DRD4 protein, human