Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuous performance test (TOVA).
Monoamine oxidase A (MAO A) is located on the X chromosome and metabolizes biogenic amines including dopamine, norepinephrine and serotonin. A functional promoter-region polymorphism of this gene has been described that has been studied in a number of mental illnesses but not in attention deficit hyperactivity disorder (ADHD). In the current study, we examined the MAO A promoter-region polymorphism initially in 133 triads and observed preferential transmission of the long alleles from 74 heterozygote mothers to ADHD probands (chi(2) = 4.37, P = 0.036, df = 1). We also examined the role of this polymorphism in a computerized continuous performance test, the TOVA. Significant differences were observed on errors of commission (chi(2) = 7.021, P = 0.008) and patients carrying the long MAO A allele made significantly more such errors. Errors of commission are a measure of impulsivity. However, following Ritalin (methylphenidate) administration the association between this polymorphism and errors of commission was markedly attenuated and no longer significant at the P < 0.05 level. We also analyzed the provisional association by the case-control design. A significant difference in allele frequency was observed between 110 male probands vs 202 male controls (Pearson chi(2) = 7.94, P = 0.047). Similarly results were obtained when 19 female probands were compared to female controls (genotype chi(2) = 21.28; P = 0.0032, 3 df and allele chi(2) = 30.88, P= 0.0007, 2 df). All three complementary approaches employed (family-based, case-control and quantitative trait design) suggest a role for the MAO A promoter-region polymorphism in conferring risk for ADHD in our patient population.
Manor
I
I
Geha Mental Health Center, Petak Tikvah, Israel.
Tyano
S
S
Mel
E
E
Eisenberg
J
J
Bachner-Melman
R
R
Kotler
M
M
Ebstein
R P
RP
D001289:Attention Deficit Disorder with Hyperactivity / Q000201:enzymology / Q000235:genetics*; D041321:Chromosomes, Human, X; D004247:DNA / Q000097:blood / Q000235:genetics; D005190:Family; D005260:Female; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D008297:Male; D008995:Monoamine Oxidase / Q000235:genetics*; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D011581:Psychological Tests; D012091:Repetitive Sequences, Nucleic Acid
D004247:DNA; D008995:Monoamine Oxidase