Attention-deficit hyperactivity disorder (ADHD) is a prevalent behavioral disorder in children and the etiology of this disorder is not clear. Molecular genetic and pharmacological studies suggest the involvement of dopaminergic and noradrenergic neurotransmitter systems in ADHD, e.g., several reports have found association between ADHD and the dopamine receptor gene DRD-4, the dopamine transporter gene DAT1, and the catecholamine clearance enzyme catechol-O-methyltransferase. Monoamine oxidase (MAO) A and B genes encode enzymes that participate in the metabolism of neurotransmitters of the dopaminergic and noradrenergic systems. MAO inhibitors have been shown to be effective in the treatment of ADHD. Our previous studies showed an association between ADHD and the DXS7 locus, which is located in close vicinity to the MAO genes on chromosome X. These findings suggest that there might be linkage between ADHD and MAO genes. To test this hypothesis, we used the transmission/disequilibrium test (TDT) to test for linkage between a VNTR polymorphism at the MAOA(CA)(n) or MAOB(GT)(n) locus and DSM-III-R-diagnosed ADHD in 82 nuclear families of the Chinese population. The TDT analysis revealed linkage between ADHD and the MAOA(CA)(n) locus (chi-square = 15.25, df = 7, P < 0.05), but not the MAOB(GT)(n) locus (chi-square = 11.18, df = 7, P > 0.05). The data showed that ADHD was in linkage with the MAOA gene and suggested that MAOA might be a susceptibility factor for ADHD.

To ascertain whether mood disorders, including bipolar and unipolar, are genetically associated with the monoamine oxidase A (MAOA) or monoamine oxidase B (MAOB) gene in the Chinese population, 132 cases of mood disorder and 88 normal controls were genotyped for the MAOA(CA)n, MAOB(GT)n, and MAOB(TG)n loci by the method of amplification fragment length polymorphism. Among 132 cases with mood disorder, eight alleles (size: 112-126 bp) of locus MAOA(CA)n, 12 alleles (size: 168-198 bp) of locus MAOB(GT)n, and nine alleles (size: 195-213 bp) of locus MAOB(TG)n were observed. Comparison of the allele frequency of the three loci showed no difference between mood disorder cases and normal controls on average. When each group was stratified into several subgroups, significant differences were found. On the MAOA(CA)n locus, the frequency of 116 bp allele was higher in the female bipolar disorder cases (0.2581) compared with that in the female unipolar disorder patients (0.1154) (Z=2.15, p<0. 05). On the MAOB(GT)n locus, the frequency of 180 bp allele was higher in bipolar disorder patients (0.1579) than that in normal controls (0.0678) (Z=2.05, p<0.05). The frequency of this allele was even higher in female bipolar disorder patients (0.1719) than that in female normal controls (0.0541). On the MAOB(TG)n locus, the frequency of 205 bp allele was higher in female bipolar disorder patients (0.6406) than that in female normal controls (0.4375) (Z=2. 17, p<0.05). For the unipolar disorder patients, the frequency of this allele was higher in female cases (0.5222) than that in male cases (0.1818) (Z=3.49, p<0.05). As for association studies, significant association between bipolar disorder and MAOB gene was detected. For the 180 bp allele of MAOB(GT)n, the relative risk (RR) of biploar versus normal control was 2.58 (p<0.05), and the RR of female bipolar disorder versus female normal control was 3.63 (p<0. 05). For the 205 bp allele of MAOB(TG)n, the RR of female bipolar disorder versus female normal control was 2.29 (p<0.05). Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:12-14, 2000.

Attention deficit hyperactivity disorder (ADHD) is a prevalent disorder in children. The etiology of this disease is not clear. Genetics studies have suggested the involvement of the dopamine DRD-4 receptor gene and dopamine transporter gene (DAT1). Clinical studies have shown that monoamine oxidase-B (MAO-B) inhibitors are effective in the treatment of ADHD. These findings suggest that monoamine oxidase (MAO) genes might be involved in the origin of ADHD. In the present work, the DXS7 locus of chromosome X, which is closely linked to MAO genes, was selected as a marker to study the possible association between ADHD and MAO genes in the Chinese population. Haplotype-based haplotype relative risk (HHRR) and the transmission disequilibrium test (TDT) methods were employed to analyze the association and the linkage disequilibrium, respectively. Significant association (X(2) = 15.86; 1 df; P < 0.001) and linkage (X(2) = 14.88; 1 df; P < 0.001) were detected between the 157-bp allele of the DXS7 locus and the DSM-III-R-diagnosed ADHD (N = 72) in trios composed of father, mother, and affected offspring. The data suggested that ADHD was associated and in linkage with DXS7 locus.

Previous studies have suggested the involvement of amyloid precursor protein (APP) in Alzheimer's disease (AD), as exons 16 and 17 of the APP gene mutations have been found in some familial AD patients. Furthermore, overexpression and deposition of the beta amyloid peptide, a proteolytic product of APP, have been considered as a pathological hallmark of Alzheimer's disease. Therefore, it is of particular interest to determine the expression of APP gene at the transcription level for better understanding of the roles of APP gene in AD pathogenesis. In this work, we employed the quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) to quantify APP mRNA transcripts in the peripheral mononuclear blood cells (PMBC) of 52 Alzheimer's patients, 28 vascular dementia (VD) patients, and 60 healthy elderly controls. The results showed that the amount (mean +/- SEM) of APP transcripts per microgram of total cDNA was 4.05 +/- 0.27, 2.73 +/- 0.33, and 2.59 +/- 0.27 amole in AD, VD, and healthy controls, respectively. There was a significant increase (P < 0.05) in the expression of APP mRNA transcripts in AD compared with that in VD or in healthy controls. Thus, our data indicated that variation of APP gene expression in PMBC might be a pathogenic source of Alzheimer's disease.

We investigated a common signal peptide polymorphism in the alpha 1-antichymotrypsin (ACT) gene in 125 sporadic Alzheimer disease (AD) patients and 141 healthy control subjects in Chinese Han population. We found no significant difference in the distribution of ACT polymorphism between AD cases and controls, and failed to detect any effects of ACT genotypes associated with AD. Thus, our data do not support the involvement of ACT polymorphism in the risk of AD in Chinese Han population. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:133-135, 2000.