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	Bhaduri N, 200515767706
Citation	Bhaduri N., Sinha S., Chattopadhyay A., Gangopadhyay P. K., Singh M. and Mukhopadhyay K. K. (2005) "Analysis of polymorphisms in the dopamine beta hydroxylase gene: association with attention deficit hyperactivity disorder in Indian children." Indian Pediatr, 42(2): 123-9.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	41 nuclear families
Predominant Ethnicity	Indian
Population	India
Gender	35 males and 6 females
Age Group	Children/Adolescents : 2.4-14 years

Detail Info

Summary	The objective is to study the association of Attention Deficit Hyperactivity Disorder (ADHD) and polymorphism in the dopamine beta hydroxylase (DBH) gene in Indian ADHD cases. Forty one ADHD cases were diagnosed as per the DSM-IV-TR criteria and evaluated by Conners' Parents and Teachers Rating Scale and Wechsler's Intelligence Scale for Children. Genomic DNA was amplified for exon 2444g/a and intron 5 (Taq I) polymorphism in the DBH gene followed by restriction fragment length polymorphism (RFLP) analysis. Haplotype-based haplotype relative risk (HHRR) was analyzed to ascertain the transmission pattern of these two polymorphisms in ADHD cases. Linkage disequilibrium (LD) between the two polymorphisms was calculated using EH+ and 2LD programs. In the limited number of samples analyzed, a slight increase in transmission of the 444a allele in ADHD subjects was observed for DBHx444g/ a. The intron 5 (Taq I) polymorphism showed no significant association with ADHD in these cases. Strong disequilibrium was observed between DBH444g/a and intron 5 (Taq I) polymorphism.
Total Sample	The total sample includes 41 nuclear Indian families having at least one ADHD child: 35 complete parent-offspring trios and 6 duos with only one parent. The age range of the probands was between 2.4 and 14 years, with 35 males and 6 females.
Sample Collection	ADHD cases were recruited from the Out-Patient Clinic of Manovikas Kendra Rehabilitation and Research Institute for the Handicapped in Kolkata.
Diagnosis Description	The subjects were diagnosed as per the Diagnostic and Statistical Manual of Mental Disorders-IV-Text revised version. All available clinical information, prenatal history, developmental milestones and family records were collected by a team of neurologist, child psychiatrist, clinical psychologist and basic researchers. The subjects were also evaluated on the following scales: (1) The Conners' Parents and Teachers Rating Scale and (2) Wechsler's Intelligence Scale for Children (WISC) for the inattention-hyperactivity level and IQ status, respectively.
Technique	Genomic DNA was amplified for exon 2x444g/a and intron 5 (Taq I) polymorphism in the DBH gene followed by restriction fragment length polymorphism (RFLP) analysis. Peripheral blood was collected from the subjects and their parents. DNA was extracted from leUnited Kingdomocytes using the standard phenol/chloroform protocol (described in the publication). PCR amplification was carried out for two polymorphisms of DBH gene, exon 2x444 g/a polymorphism and intron 5 (Taq I) polymorphism. PCR amplification for both polymorphisms were carried out using Perkin Elmer thermal cycler in a final reaction volume of 40 uL containing 75-100ng of genomic DNA, 20 pmoles of each primer, 0.2 U Taq polymerase, 200 uM dNTP mix, 5% glycerol and 10 mM Tris buffer (Genei) with 50 mM KCl and 1.5 mM MgCl₂. DBHx444g (allele A1) is cleaved by the restriction endonuclease EcoN I yielding two fragments of 169 and 38-bp respectively; The Taq I polymorphism in intron 5 of the DBH gene refers to a gain of restriction digestion site, which can be cleaved by the endonuclease Taq I. The A1 allele for this polymorphism is the undigested 464-bp PCR product, whereas, A2 allele, on digestion with Taq I, yields two fragments of 300 and 164-bp, respectively.
Analysis Method	They used the Haplotype-based haplotype relative risk (HHRR) design to ascertain association between ADHD and transmission of genetic polymorphisms. The EH+ program, version 1.2 was utilized to estimate the haplotype frequencies for the different alleles of DBH444 g/a and intron 5 (Taq I) polymorphism. Subsequently, they used the 2LD program to compute the disequilibria (D&D') values for DBH444 g/a and intron 5 (Taq I) polymorphism.
Result Description	In the limited number of samples analyzed, a slight increase in transmission of the 444a allele in ADHD subjects was observed for DBH444g/ a. The intron 5 (Taq I) polymorphism showed no significant association with ADHD in these cases. Strong disequilibrium was observed between DBH444g/a and intron 5 (Taq I) polymorphism.

Other variant reported by this study (count: 2)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
DBH intron5 C/T TaqI	C/T		allelic HHRR P-value=0.7082, X²(df=1)=0.14, RR=0....... allelic HHRR P-value=0.7082, X²(df=1)=0.14, RR=0.93 More...	suggested lack of significant association between transmission of this polymorphism and ADHD	Non-significant
DBH exon2 444G/A EcoNI	G/A		allelic HHRR P-value=0.3744, X²(df=1)=0.789, RR=0...... allelic HHRR P-value=0.3744, X²(df=1)=0.789, RR=0.86 More...	the data was not statistically significant	Non-significant

Genes reported by this study (count: 1)