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	Aureli A, 200819144284
Citation	Aureli A., Sebastiani P., Del Beato T., Marimpietri A., Melillo V., Sechi E. and Di Loreto S. (2008) "Investigation on the possible relationship existing between the HLA-DR gene and attention deficit hyperactivity disorder and/or mental retardation." Int J Immunopathol Pharmacol, 21(4): 985-91.
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	81 children (37 with ADHD, and 44 with MR), 100 controls
Predominant Ethnicity	Caucasian
Population	Italy
Age Group	Children/Adolescents : 2-18 year, mean age: 9.84

Detail Info

Summary	This study examines the possible relationship existing between the HLA-DR gene and attention defidt hyperactivity disorder (ADHD) and/or mental retardation (MR). The diagnosis of ADHD and mental retardation were established through clinical interviews with the parents, children and teachers, according to the criteria in DSM-IV. HLA-DRB1 genotyping was performed both by polymerase chain reaction-sequence specific primers (PCR-SSP) and by sequence based typing (SBT) in a cohort of 81 affected children and a sample of 100 healthy controls. Here, they report a positive assodation of HLADR4 with ADHD but not with MR. The study adds confirmation to the role of the HLA-DRBl in the etiology of some types of childhood neuropsychiatric illnesses.
Total Sample	Eighty-one children (male and female) participated in this study. They were divided into two principal groups: one of 44 children affected by mental retardation and the other of 37 ADHD children with or without comorbidity. The patients were aged from 2 to 18 years, with a mean age of 9.84 years and of Caucasian origin. A sample of 100 healthy blood donors took part in the research as controls and were matched with the study groups.
Sample Collection	All the children were recruited and tested at the Clinic of Children's Neuropsychiatric Diseases in L'Aquila, Italy.
Diagnosis Description	ADHD or mental retardation were diagnosed by clinicians using DSM-IV criteria. The Kiddie-SADS Present and Lifetime Version (K-SADS-PL) and the Conners' Rating Scales (CRS) were used to collect additional infonnation on the diagnosis.
Technique	EDTA peripheral blood samples were used for DNA extraction by a QIAamp DNA blood kit (Qiagen, Hilden, Germany). After the extraction, the quality of the DNA was tested through a spectrophotometer. HLA-DRBl genotyping was performed by polymerase chain reaction-sequence specific primer (PCR-SSP) method using twenty-four primer mixes for HLA-DR (Biotest HLA-SSP; Dreieich, Germany). PCR amplifications were carried out in a GeneAmp PCRsystem 9600 (Perkin-Elmer, Foster City, CA, USA). The DRB 1x04 alleles among ADHD cases were defined by sequence-based typing (SBT). Exon 2 of the HLA-DR gene was amplified by polymerase chain reaction and sequenced with the Big Dye Terminator Chemistry (Applied Biosystems, Foster City, CA) in both orientations on an ABl Prism 3100 Genetic Analyzer (PE App1ied Biosystems). Sequences were analyzed with the ASSIGN SBT v 3.5 software (Conexio Genomics, App1ecross, Western Australia, Australia).
Analysis Method	Differences between HLA-DRBl allele frequencies in cases and controls were evaluated using Fisher exact probability test, and odds ratio (OR, including the 95% Cl interva1s) was used as the measure of association. The level of statistical significance was defined as p<0.05. The Bonferroni adjustment was used to control the type 1 error in multiple tests.
Result Description	Here, they report a positive assodation of HLADR4 with ADHD but not with MR. The study adds confirmation to the role of the HLA-DRBl in the etiology of some types of childhood neuropsychiatric illnesses.

Other variant reported by this study (count: 1)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
HLA-DRB1 alleles01-10	allele 1-10		Fisher exact probability test P-value=0.45, OR=0.61 for DRB1...... Fisher exact probability test P-value=0.45, OR=0.61 for DRB101, Fisher exact probability test P-value=0.34, OR=1.59 for DRB102, Fisher exact probability test P-value=0.81, OR=0.84 for DRB103, Fisher exact probability test P-value=0.001, corrected P-value=0.01, OR=4.81 for DRB104, Fisher exact probability test P-value=0.03, OR=0.51 for DRB105, Fisher exact probability test P-value=0.71, OR=0.85 for DRB106, Fisher exact probability test P-value=0.28, OR=1.57 for DRB107, Fisher exact probability test P-value=0.70, OR=1.36 for DRB108 More...	HLA-DR4 frequencies of the ADHD group were significantly different from controls, and frequencies of other HLA-DRB1 alleles did not differ significantly	Significant

Genes reported by this study (count: 1)