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.
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.
Domschke
Katharina
K
Department of Genetics, Trinity College Dublin, Ireland.
Sheehan
Karen
K
Lowe
Naomi
N
Kirley
Aiveen
A
Mullins
Celine
C
O'sullivan
Roderick
R
Freitag
Christine
C
Becker
Tim
T
Conroy
Judith
J
Fitzgerald
Michael
M
Gill
Michael
M
Hawi
Ziarih
Z
D000328:Adult; D000483:Alleles; D001289:Attention Deficit Disorder with Hyperactivity / Q000201:enzymology / Q000235:genetics*; D002648:Child; D018900:Dinucleotide Repeats / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007494:Ireland; D015810:Linkage Disequilibrium; D008297:Male; D018598:Minisatellite Repeats / Q000235:genetics; D008995:Monoamine Oxidase / Q000235:genetics*; D009679:Nuclear Family; D012196:Review Literature as Topic
D008995:Monoamine Oxidase