Association analysis of the monoamine oxidase A and B genes with attention deficit hyperactivity disorder (ADHD) in an Irish sample: preferential transmission of the MAO-A 941G allele to affected children.

Abstract

Pharmacological and genetic studies suggest the importance of the dopaminergic, serotonergic, and noradrenergic systems in the pathogenesis of attention deficit hyperactivity disorder (ADHD). Monoamine oxidases A and B (MAO-A and MAO-B) degrade biogenic amines such as dopamine and serotonin and thereby control the levels of these neurotransmitters in the central nervous system. We examined four polymorphisms in the MAO-A gene (30 bp promoter VNTR, CA microsatellite in intron 2, 941G/T SNP in exon 8, and A/G SNP in intron 12) as well as two markers in the MAO-B gene (CA microsatellite in intron 2 and T/C SNP in intron 13) for association with ADHD in an Irish sample of 179 nuclear families. TDT analysis of the examined MAO-A markers revealed a significant association of the more active MAO-A 941G allele with the disorder (chi2 = 5.1, P = 0.03, OR = 1.7). In addition, haplotype analysis revealed a significantly increased transmission of a haplotype consisting of the shorter allele of the promoter VNTR (allele 1), the 6-repeat allele of the CA microsatellite and the G-allele of the 941G/T SNP (famhap global statistic 34.54, P = 0.01) to ADHD cases. No significant distortion in the number of transmitted alleles was observed between the two examined MAO-B polymorphisms and ADHD. These findings suggest the importance of the 941G/T MAO-A polymorphism in the development of ADHD at least in the Irish population.

• Authors: Katharina Domschke, Karen Sheehan, Naomi Lowe, Aiveen Kirley, Celine Mullins, Roderick O'sullivan, Christine Freitag, Tim Becker, Judith Conroy, Michael Fitzgerald, Michael Gill, Ziarih Hawi
• Journal: American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics (Am J Med Genet B Neuropsychiatr Genet) Vol. 134B Issue 1 Pg. 110-4 (Apr 05 2005) ISSN: 1552-4841 [Print] United States
• PMID: 15717295 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2005 Wiley-Liss, Inc.

Chemical References

• Monoamine Oxidase

Topics

• Adult
• Alleles
• Attention Deficit Disorder with Hyperactivity (enzymology, genetics)
• Child
• Dinucleotide Repeats (genetics)
• Female
• Genotype
• Haplotypes
• Humans
• Ireland
• Linkage Disequilibrium
• Male
• Minisatellite Repeats (genetics)
• Monoamine Oxidase (genetics)
• Nuclear Family
• Review Literature as Topic