ADHDgene Database

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Large-scale studies

Data Summary

Published Variant
- SNP: 1391
- CNV: 398
- Others: 173
Published Gene: 359
Published Region: 128
Pathway by PBA: 8
Study: 361

Study Report

Basic Info

Reference	Leung PW, 200515578612
Citation	Leung P. W., Lee C. C., Hung S. F., Ho T. P., Tang C. P., Kwong S. L., Leung S. Y., Yuen S. T., Lieh-Mak F., Oosterlaan J., Grady D., Harxhi A., Ding Y. C., Chi H. C., Flodman P., Schuck S., Spence M. A., Moyzis R. and Swanson J. (2005) "Dopamine receptor D4 (DRD4) gene in Han Chinese children with attention-deficit/hyperactivity disorder (ADHD): increased prevalence of the 2-repeat allele." Am J Med Genet B Neuropsychiatr Genet, 133B(1): 54-6.
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	32 Han Chinese boys and 247 DRD4 genotypes from five Han Chinese community samples surveyed previously
Predominant Ethnicity	Mongoloid
Population	China
Gender	32 male probands
Age Group	Children/Adolescents : 6-15 years (mean=9.1, SD=1.9) for cases

Detail Info

Summary	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 DRD47R allele. Instead, they observed a significantly increased prevalence of the 2-repeat (2R) allele in this clinical sample (33%) compared to ethnically-matched controls (20%). This approximately 1.65-fold increase of the 2R allele in their 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, they propose that the observed increased prevalence of the 2R allele in the 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. They hypothesize that an increased frequency of any non-4R allele may define the association of the DRD4 gene with ADHD that holds across ethnicity.
Total Sample	Thirty-seven Han Chinese children with a clinical diagnosis of ADHD were recruited from two child psychiatric clinics in Hong Kong. The clinical ADHD diagnosis of five children was not confirmed by the DISC-IV. Consequently, the group of DISC-confirmed ADHD probands consisted of 32 Han Chinese boys whose age ranged from 6 to 15 years (mean=9.1, SD=1.9) and whose verbal IQs from 75 to 145 (mean=109, SD=18). 247 DRD4 genotypes from five Han Chinese community samples surveyed previously (San Francisco (N=49), Taiwan (N=43), Liaoning (N=67), Qingdao (N=35), and Guangdong (N=43)) [Chang et al., 1996; Ding et al., 2002]
Sample Collection	Thirty-seven Han Chinese children with a clinical diagnosis of ADHD were recruited from two child psychiatric clinics in Hong Kong.
Diagnosis Description	The parents of these children were interviewed by the Diagnostic Interview Schedule for Children-Version IV (DISC-IV) which yield Diagnostic and Statistical Manual of Mental Disorders-4th Edition (DSM-IV) diagnoses for children and adolescents [Shaffer et al., 2000]. In this study, an English to Chinese translation of the Parent version was used and four modules on anxiety disorders, mood disorders, disruptive behavior disorders, and alcohol/substance abuses were administered. The DISC-IV diagnosis of ADHD was used to confirm the clinical diagnosis of the local clinicians in Hong Kong and to ensure standardization of case definition and compatibility with other studies of ADHD. Fourteen of them (44%) met the criteria for the combined type, 10 (31%) for the inattentive type, and 8 (25%) for the hyperactive-impulsive type.
Technique	Ten c.c. of venuous blood were taken from these 37 children for genotying. Blood samples or DNA were sent to the Department of Biochemistry, University of California, Irvine, and genotyping was conducted as described previously [Ding et al., 2002; Grady et al., 2003].
Analysis Method	Chi-square analysis was perfomred to compare DRD4 allele frequencies (2R Vs. Non-2R Alleles) between 32 Han Chinese ADHD probands and 247 ethnically-matched community controls.
Result Description	None of them had a DRD47R allele. Instead, they observed a significantly increased prevalence of the 2-repeat (2R) allele in this clinical sample (33%) compared to ethnically-matched controls (20%). This approximately 1.65-fold increase of the 2R allele in their 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, they propose that the observed increased prevalence of the 2R allele in the 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. They hypothesize that an increased frequency of any non-4R allele may define the association of the DRD4 gene with ADHD that holds across ethnicity.

Other variant reported by this study (count: 1)

Genes reported by this study (count: 1)