Lack of association of dopamine D4 receptor gene polymorphisms with ADHD subtypes in a population sample of twins

Attention-deficit hyperactivity disorder (ADHD) is a common, highly heritab le syndrome of childhood characterized by problems with inattention, hypera ctivity, and impulsivity. A variety of case control and family-based transm ission distortion genetic studies of ADHD have focused on the possible invo lvement of polymorphisms of the DRD4 receptor gene. The majority of studies have examined the association of variously defined ADHD with an exon 3 pol ymorphism containing a variable number of imperfect 48 base pair repeats. R ecently, McCracken et al, [2000: Mol Psych 5:531-536] reported an associati on of the DSM-IV primarily inattentive ADHD subtype with a 5' 120 base pair repeat polymorphism in the DRD4 gene, In this report, we test for the poss ible association of these two polymorphisms with population-derived samples of DSM-IV ADHD subtypes, Furthermore, we extend previous studies by testin g for associations with ADHD subtypes derived from latent-class analysis of interview responses. In contrast to most, but not all, previous studies, w e failed to demonstrate any significant association of the exon 3 7-repeat allele with ADHD, Nor did we replicate the association of the 5'120 base pa ir repeat polymorphism, We do find a significant association of the exon 3 3-repeat allele with a novel talkative/impulsive latent-class-defined subty pe of ADHD, (C) 2001 Wiley-Liss. Inc.