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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
Author(s) -
Domschke Katharina,
Sheehan Karen,
Lowe Naomi,
Kirley Aiveen,
Mullins Celine,
O'Sullivan Roderick,
Freitag Christine,
Becker Tim,
Conroy Judith,
Fitzgerald Michael,
Gill Michael,
Hawi Ziarih
Publication year - 2005
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.30158
Subject(s) - allele , genetics , haplotype , monoamine oxidase a , biology , attention deficit hyperactivity disorder , snp , single nucleotide polymorphism , allele frequency , genotype , gene , serotonin , medicine , psychiatry , receptor
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 (χ 2 = 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. © 2005 Wiley‐Liss, Inc.