TY - JOUR
T1 - Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD)
T2 - Preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuous performance test (TOVA)
AU - Manor, I.
AU - Tyano, S.
AU - Mel, E.
AU - Eisenberg, J.
AU - Bachner-Melman, R.
AU - Kotler, M.
AU - Ebstein, R. P.
N1 - Funding Information:
This research was supported by a grant from the Israeli Ministry of Health.
PY - 2002
Y1 - 2002
N2 - 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 (X2 = 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 (X2 = 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 X2 = 7.94, P = 0.047). Similarly results were obtained when 19 female probands were compared to female controls (genotype X2 = 21.28; P = 0.0032, 3 df and allele X2 = 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.
AB - 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 (X2 = 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 (X2 = 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 X2 = 7.94, P = 0.047). Similarly results were obtained when 19 female probands were compared to female controls (genotype X2 = 21.28; P = 0.0032, 3 df and allele X2 = 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.
KW - Association
KW - Attention deficit hyperactivity disorder (ADHD)
KW - Complex genetic
KW - Continuous performance test
KW - Endophenotype
KW - Monoamine oxidase A
KW - Neuropsychological functioning
KW - Polymorphism
KW - Promoter
KW - QTL
KW - TOVA
KW - Transmission disequilibrium test
UR - http://www.scopus.com/inward/record.url?scp=0036024267&partnerID=8YFLogxK
U2 - 10.1038/sj.mp.4001037
DO - 10.1038/sj.mp.4001037
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AN - SCOPUS:0036024267
SN - 1359-4184
VL - 7
SP - 626
EP - 632
JO - Molecular Psychiatry
JF - Molecular Psychiatry
IS - 6
ER -