Evaluation of potential gene–gene interactions for attention deficit hyperactivity disorder in the Han Chinese population

Several lines of evidence suggest that attention-deficit/hyperactivity disorder (ADHD) is a polygenic disorder produced by the interaction of several genes with minor effects. To explore potential gene–gene interactions among candidate genes for ADHD, we studied the dopamine D2 receptor (DRD2), dopamine D4 receptor (DRD4), dopamine transporter (DAT1), and catechol-O-methyltransferase (COMT) genes in the Han Chinese population. A sample of 340 children with ADHD was diagnosed according to the DSM-IV criteria. We also recruited 226 unrelated controls. Identified polymorphisms included a 48-base-pair-repeat in Exon 3 of DRD4, a 40-base-pair-repeat in the 3′ untranslated region of DAT1, a restriction-fragment-length polymorphism at codon 158 of COMT, and a −241A > G transition in the promoter of DRD2. Associations of polymorphisms with ADHD and its subtypes were examined by comparing allele frequencies between probands and controls. Binary logistic regression analysis was used to examine the potential gene–gene interactions. Binary logistic regression analysis with the sample of refined phenotypes showed that male gender and long-repeat genotypes of DRD4 and DAT1 were independent risk factors for ADHD. We found no evidence for gene–gene interactions among the candidate genes studied. The present study suggests that dopamine candidate genes are associated with increased vulnerability to ADHD in the Han Chinese population. Copyright © 2006 Wiley-Liss, Inc.