| Summary |
In the current study, they examined the MAOA promoter-region polymorphism initially in 133 triads and observed preferential transmission of the long alleles from 74 heterozygote mothers to ADHD probands (P=0.036). They also examined the role of this polymorphism in a computerized continuous performance test, the TOVA. Significant differences were observed on errors of commission (P=0.008) and patients carrying the long MAOA 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. They 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 P=0.047). Similarly results were obtained when 19 female probands were compared to female controls (genotype P=0.0032, 3 df and allele P=0.0007, 2 df). All three complementary approaches employed (family-based, case-control and quantitative trait design) suggest a role for the MAOA promoter-region polymorphism in conferring risk for ADHD in current patient population. |
| Total Sample |
Linkage between the MAOA promoter region polymorphism and ADHD was tested by using the transmission disequilibrium test in a group of 133 triads (proband and both parents). A case-control approach was also employed in a sample of 110 male ADHD probands compared to 202 control subjects and a sample of 19 female ADHD probands compared to 265 female control subjects. ADHD cases and parents were recruited from the greater Tel-Aviv (Petak Tikvah) municipal area (n=133 families). The percentage of probands with ADHD combined type was 68.2%, inattentive 30.6% and 1.2% impulsive. Twenty-seven percent of the probands had comorbid ODD/CD. |
| Sample Collection |
ADHD cases and parents were recruited from the greater Tel-Aviv (Petak Tikvah) municipal area (n=133 families). Subjects were all clinical referrals from hospital neurologists, school psychologists and parents. Families included all diagnosed ADHD children who had two biological parents. The Ethics Committee of the Israeli Health Ministry approved this study and written informed consent was obtained from participating subjects. |
| Diagnosis Description |
ADHD criteria followed DSM-IV guidelines that recognize three types of ADHD: ADHD-Predominantly Inattentive (Type I), ADHD-Predominantly Hyperactive Impulsive (Type II), and ADHD-Combined Type (III). Informants were the parents, the teacher, and the proband. The parents and the proband underwent a thorough, albeit not standardized, clinical interview, which included as a separate item all DSM-IV criteria for ADHD and Conduct Disorder. Two scales, the abbreviated Conners Rating Scales and the Child Behavior Checklist, were also employed. Consensus diagnoses were made according to DSM-IV ADHD or either with or without comorbidity. These DSM-IV diagnoses were based on all available clinical information and the Child Behaviour Checklist and the Conners Parents and Teachers Rating Scales. When the Conners teachers scale was not available, teachers were contacted by telephone and interviewed. The ADHD subjects were also administered the Test Of Variables of Attention (TOVA), which is a computerized Continuous Performance Test. Cases with a primary diagnosis of Pervasive Developmental Disorder, physical handicap, psychosis, mental retardation, epilepsy, hyperthyroidism, evidence or history of child abuse, adoption were excluded. Children with an IQ less than 80 were excluded. IQ was assessed using the Wechsler Intelligence Scale for Children-Revised. |
| Technique |
DNA was extracted from frozen blood samples using the phenol procedure or from fresh blood using a MasterPure kit (Epicentre Technologies, Madison, WI, USA). From some individuals, from whom blood sample could not be obtained, DNA was obtained from buccal smears again using the MasterPure kit. The promoter region polymorphism was characterized using a PCR procedure. |
| Analysis Method |
The transmission disequilibrium test was used to analyze transmission from heterozygote mothers to ADHD probands. Subjects were grouped into two genotype classes: 2 (only one case) & 3 repeats (short) and 4 & 5 repeats (long). In this analysis therefore the 2 and 3 alleles were pooled as 'short' and the 4 and 5 alleles as 'long'. The rare occurrence of the 2 and 5 alleles made superfluous the use of the ETDT statistic. The Kruskal-Wallis one-way ANOVA is the distribution-free (or nonparametric) analogue of the parametric ANOVA and was used to group TOVA scores by genotype. |
| Result Description |
The most common alleles are the 3 and 4 repeats that account for 96% of the alleles. The 2 and 5 alleles are relatively rare. Possible preferential transmission of the MAOA promoter region polymorphism from heterozygote mothers to the proband was examined using the TDT design. There is significant transmission of the long (4 & 5) alleles (P=0.036). Similar results were obtained if only transmission of the common 3 and 4 repeat alleles (excluding the 5 repeat) was considered (P=0.09). A significant difference in allele frequency was observed (Pearson P=0.047). Similar results were obtained with the smaller group of female probands compared to a group of female controls (genotype P=0.0032, allele P=0.0007). |
Hot Results
Basic Info
Detail Info