Investigation of the dopamine D5 receptor gene (DRD5) in adult attention deficit hyperactivity disorder.
Several lines of evidence from neuroimaging, pharmacology and genetics support the involvement of the dopaminergic system in the etiology of Attention Deficit Hyperactivity Disorder (ADHD). Previous candidate gene studies have investigated the association between a dinucleotide (CA)(n) repeat polymorphism, located 18.5 kb from the start codon of the DRD5 gene, and ADHD. Association between the 148 bp allele and ADHD has been reported in some studies, however replication of the finding has not been consistent. We tested for an association between the (CA)(n) repeat and adult ADHD in a sample comprised of 119 families with adult ADHD probands and 88 unrelated adult ADHD cases with a corresponding number of controls matched for age, ethnicity and sex. In the family sample we found a non-significant trend for association between the 148 bp allele and ADHD (Z=1.91, p=0.055). An excess of non-transmissions was detected for the 150 and 152bp alleles (Z=-2.26, p=0.023; Z=-2.20, p=0.028). Quantitative analysis performed using the Brown Attention Deficit Disorder Scale (BADDS) showed association between the 150 bp allele and lower total score (p=0.011), and lower effort (p=0.008), activation (p=0.008) and attention (p=0.01) cluster scores. We did not replicate association findings in the case-control group, likely due to the lack of statistical power of this sample. Our findings add to the literature suggesting DRD5 (CA)(n) repeat has a modest effect in modulating susceptibility to adult ADHD but further studies are required.
Squassina
Alessio
A
Neurogenetics Section, Centre for Addiction and Mental Health, Department of Psychiatry, University of Toronto, 250 College Street, Toronto, ON M5T 1R8, Canada. cortgen@yahoo.it
Lanktree
Matthew
M
De Luca
Vincenzo
V
Jain
Umesh
U
Krinsky
Marilee
M
Kennedy
James L
JL
Muglia
Pierandrea
P
D000328:Adult; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics*; D016022:Case-Control Studies; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D050641:Receptors, Dopamine D5 / Q000235:genetics*
D050641:Receptors, Dopamine D5