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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	El-Tarras, A. E., 201223076524
Citation	El-Tarras, A. E., A. A. Alsulaimani, N. S. Awad, N. Mitwaly, M. M. Said and A. M. Sabry (2012). "Association study between the dopamine-related candidate gene polymorphisms and ADHD among Saudi Arabia population via PCR technique." Mol Biol Rep 39(12): 11081-11086.
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	120 cases and 160 controls
Predominant Ethnicity
Population	Saudi
Age Group	Children/Adolescents

Detail Info

Summary	The aim of the present study is to investigate the association between ADHD and polymorphisms of MAOA 30 bp-promoter VNTR and DAT1 40 bp 3' UTRVNTR in Saudi population. PCR technique was employed to detect polymorphisms of MAOA and DAT1 genes in a sample of 120 ADHD subjects and 160 controls. Alleles and genotypes frequencies for both of MAOA and DAT1 polymorphisms were compared among ADHD subjects against controls. Association between ADHD and alleles as well as genotypes for each studied polymorphisms was tested by odds ratio (OR) test and the magnitude of this association was estimated by 95 % confidence interval (95 % CI). A significant association was found between two MAOA genotypes 3/4 and 3/2 with ADHD (P < 0.01, OR = 3, 4.9) as a risk effect. No significant association was found with MAOA alleles. Among DAT1 polymorphisms two alleles (7 and 11 repeats) (P < 0.01, OR = 2.5 and 3.3) as well as two genotypes (11/11 and 11/7) (P < 0.01, OR = 4, 3) showed significant association with ADHD as a risk effect. On the contrary, 9 and 10 repeats revealed significant association as a protective effect as well as 10/10 and 10/9 genotypes. These findings support the hypothesis that some of the MAOA and DAT1 polymorphisms have a causative role in the development of ADHD in the Saudi population. Another polymorphism did not give rise to support this hypothesis.
Total Sample	Total 120 pure ADHD children between the ages 6-12 years from Pediatric Hospital and Prince Mansour Hospital at Taif city were included in the present study. In addition, 160 healthy age matched controls were recruited. All subjects were clinical referrals from hospital neurologists. Consensus diagnoses were made according to DSMIV ADHD. Two scales, the abbreviated Conners Parent and Teacher Rating Scales and the child Behavior Checklist, were also employed. Non Saudi subjects as well as Autism cases were excluded from the study. No other neurological or behavioral disorders were identified.
Sample Collection	Total 120 pure ADHD children between the ages 6-12 years from Pediatric Hospital and Prince Mansour Hospital at Taif city were included in the present study. In addition, 160 healthy age matched controls were recruited. All subjects were clinical referrals from hospital neurologists.
Diagnosis Description	Consensus diagnoses were made according to DSMIV ADHD. Two scales, the abbreviated Conners Parent and Teacher Rating Scales and the child Behavior Checklist, were also employed. Non Saudi subjects as well as Autism cases were excluded from the study. No other neurological or behavioral disorders were identified.
Technique	MAOA 30 bp-promoter VNTR polymorphic was characterized using PCR procedure; Genotyping of DAT1 40-bp VNTR in the 3'UTR was carried out using a PCR procedure.
Analysis Method	In this case control study the allele frequencies of DAT1 and MAOA studied polymorphisms were estimated by direct counting and the difference in allele and genotype frequencies between the ADHD subjects and controls was tested using the odds ratio test. The magnitude of this association was estimated by 95 % confidence interval (95 % CI).
Result Description	A significant association was found between two MAOA genotypes 3/4 and 3/2 with ADHD (P < 0.01, OR = 3, 4.9) as a risk effect. No significant association was found with MAOA alleles. Among DAT1 polymorphisms two alleles (7 and 11 repeats) (P < 0.01, OR = 2.5 and 3.3) as well as two genotypes (11/11 and 11/7) (P < 0.01, OR = 4, 3) showed significant association with ADHD as a risk effect. On the contrary, 9 and 10 repeats revealed significant association as a protective effect as well as 10/10 and 10/9 genotypes. These findings support the hypothesis that some of the MAOA and DAT1 polymorphisms have a causative role in the development of ADHD in the Saudi population. Another polymorphism did not give rise to support this hypothesis. This is the first report investigated the association between MAOA and DAT1 polymorphism at molecular level in Saudi Arabia population as well as Arab world. Therefore further studies are needed to generalize obtained results at Saudi Arabia.

Other variant reported by this study (count: 2)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
SLC6A3 3'-UTR VNTR			allelic P-value<0.01, OR=2.5, CI=1.4-4.6 for 7R; P-value<0.0...... allelic P-value<0.01, OR=2.5, CI=1.4-4.6 for 7R; P-value<0.01, OR=0.4, CI=0.2-0.6 for 9R; P-value<0.01, OR=0.4, CI=0.3-0.5 for 10R; P-value<0.01, OR=3.3, CI=2.3-4.8 for 11R; genotypic P-value<0.01, OR=0.3, CI=0.1-0.6 for 10/10; P-value<0.01, OR=0.3, CI=0.2-0.5 for 10/9; P-value<0.01, OR=4, CI=2.1-7.9 for 11/11; P-value=0.01, OR=3, CI=1.4-7 for 11/7; P-value=0.4, OR=1.4, CI=0.7-2.8 for 11/10; P-value=0.08, OR=2.1, CI=0.9-5.1 for 10/7 More...	Among DAT1 allele and genotypes there were statistically strong association between 7 and 11 repeats and ADHD (OR: 2.5 and 3.3) respectively. While, repeats 9 and 10 seems to have protective effects. 11/11 and 11/7 genotypes, revealed strong significant associated with ADHD (OR = 4 and 3) respectively.	Significant
MAOA promoter VNTR			allelic P-value=0.1, OR=1.4, CI=0.9-2.1 for allele 2; P-valu...... allelic P-value=0.1, OR=1.4, CI=0.9-2.1 for allele 2; P-value=0.07, OR=0.7, CI=0.5-1.0 for allele 3; P-value=0.5, OR=1.1, CI=0.8-1.6 for allele 4; P-value=0.9, OR=1, CI=0.7-1.3 for allele 5; P-value=0.6, OR=0.9, CI=0.7-1.3 for short allele; P-value=0.6, OR=1.1, CI=0.8-1.5 for long allele; genotypic P-value=0.01, OR=0.4, CI=0.2-0.8 for 3/3; P-value=0.5, OR=1.3, CI=0.5-3.5 for 3/5; P-value<0.01, OR=3, CI=1.3-7.0 for 3/4; P-value<0.01, OR=4.9, CI=2.4-11.1 for 4/4; P-value=0.7, OR=0.9, CI=0.5-1.6; P-value=0.8, OR=0.9, CI=0.4-2.0 for 5/5; P-value=0.8, OR=0.9, CI=0.4-2.0 for 4/5; P-value=0.3, OR=0.6, CI=0.2-1.4 More...	MAOA genotypes 3/4 and 3/2 showed highly significant association with ADHD (OR = 3 and 4.9) respectively, while no significant association was fond with MAOA alleles. It is also worth to mention that the P value for association with genotype 3 was 0.07 which is not very far from the level of significance.	Significant

Genes reported by this study (count: 2)

Gene	Statistical Values/Author Comments	Result of Statistical Analysis
SLC6A3	These findings support the hypothesis that some of the MAOA ...... These findings support the hypothesis that some of the MAOA and DAT1 polymorphisms have a causative role in the development of ADHD in the Saudi population. More...	Significant
MAOA	These findings support the hypothesis that some of the MAOA ...... These findings support the hypothesis that some of the MAOA and DAT1 polymorphisms have a causative role in the development of ADHD in the Saudi population. More...	Significant