title: Dopamine receptor D4 (DRD4) gene in Han Chinese children with attention-deficit/hyperactivity disorder (ADHD): increased prevalence of the 2-repeat allele.
abstract: There is an increased prevalence of the 7-repeat (7R) allele of the dopamine receptor D4 (DRD4) gene in attention-deficit/hyperactivity disorder (ADHD). However, the population prevalence of the 7R allele varies considerably across ethnicity and is very low in Asians. To test whether this 7R allele/ADHD association still held in a Chinese clinical sample, 32 Han Chinese children with a confirmed ADHD diagnosis and normal IQ who were methylphenidate-responders were genotyped. None of them had a DRD4 7R allele. Instead, we observed a significantly increased prevalence of the 2-repeat (2R) allele in this clinical sample (33%) compared to ethnically-matched controls (20%) (chi(2)(1d.f.) = 5.90, P = 0.015). This approximately 1.65-fold increase of the 2R allele in our probands is close to the observed increase of the 7R allele in European-ancestry ADHD children. Recent genetic studies have indicated that the 2R allele in Asians is likely derived from the 7R allele. Further, available biochemical data indicate that both the 2R and 7R protein have blunted responses to dopamine compared to the 4R protein. Based on these results, we propose that the observed increased prevalence of the 2R allele in our Han Chinese ADHD probands is still consistent with the 7R allele hypothesis of ADHD in European-ancestry children. Recent studies have suggested that any variant from the conserved ancestral 4R allele might potentially alter biochemistry/phenotype. We hypothesize that an increased frequency of any non-4R allele may define the association of the DRD4 gene with ADHD that holds across ethnicity. The present findings, however, obtained with a small ADHD sample size, should be replicated.
authors.affiliation: Department of Psychology, The Chinese University of Hong Kong, Hong Kong. pleung@cuhk.edu.hk
authors.forename: Patrick W L
authors.initials: PW
authors.lastname: Leung
authors.forename: C C
authors.initials: CC
authors.lastname: Lee
authors.forename: S F
authors.initials: SF
authors.lastname: Hung
authors.forename: T P
authors.initials: TP
authors.lastname: Ho
authors.forename: C P
authors.initials: CP
authors.lastname: Tang
authors.forename: S L
authors.initials: SL
authors.lastname: Kwong
authors.forename: S Y
authors.initials: SY
authors.lastname: Leung
authors.forename: S T
authors.initials: ST
authors.lastname: Yuen
authors.forename: F
authors.initials: F
authors.lastname: Lieh-Mak
authors.forename: Jaap
authors.initials: J
authors.lastname: Oosterlaan
authors.forename: Deborah
authors.initials: D
authors.lastname: Grady
authors.forename: Ante
authors.initials: A
authors.lastname: Harxhi
authors.forename: Y C
authors.initials: YC
authors.lastname: Ding
authors.forename: H C
authors.initials: HC
authors.lastname: Chi
authors.forename: Pamela
authors.initials: P
authors.lastname: Flodman
authors.forename: Sabrina
authors.initials: S
authors.lastname: Schuck
authors.forename: M Anne
authors.initials: MA
authors.lastname: Spence
authors.forename: Robert
authors.initials: R
authors.lastname: Moyzis
authors.forename: James
authors.initials: J
authors.lastname: Swanson
mesh_terms: D000293:Adolescent; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D002648:Child; D002681:China; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D050638:Receptors, Dopamine D4
chemical_list: C493599:DRD4 protein, human; D017448:Receptors, Dopamine D2; D050638:Receptors, Dopamine D4