Skip to main content
Top
Published in: BMC Psychiatry 1/2007

Open Access 01-12-2007 | Research article

Association study between the monoamine oxidase A gene and attention deficit hyperactivity disorder in Taiwanese samples

Authors: Xiaohui Xu, Keeley Brookes, Chih-Ken Chen, Yu-Shu Huang, Yu-Yu Wu, Philip Asherson

Published in: BMC Psychiatry | Issue 1/2007

Login to get access

Abstract

Background

Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable disorder of childhood characterized by inattention, hyperactivity and impulsivity. Molecular genetic and pharmacological studies suggest the involvement of the dopaminergic, serotonergic and noradrenergic neurotransmitter systems in the pathogenesis of ADHD. Monoamine oxidase A (MAO-A) encodes an enzyme that degrades biogenic amines, including neurotransmitters such as norepinephrine, dopamine and serotonin. In this study we examined a 30 bp promoter variable number tandem repeat (VNTR) and a functional G/T single nucleotide polymorphism (SNP) at position 941 in exon 8 (941G/T) of MAO-A for association with ADHD in a Taiwanese sample of 212 ADHD probands.

Methods

Within-family transmission disequilibrium test (TDT) was used to analyse association of MAO-A polymorphisms with ADHD in a Taiwanese population.

Results

A nominally significant association was found between the G-allele of 941G/T in MAO-A and ADHD (TDT: P = 0.034. OR = 1.57). Haplotype analysis identified increased transmission of a haplotype consisting of the 3-repeat allele of the promoter VNTR and the G-allele of the 941G/T SNP (P = 0.045) to ADHD cases which the strong association with the G-allele drove.

Conclusion

These findings suggest the importance of the 941G/T MAO-A polymorphism in the development of ADHD in the Taiwanese population. These results replicate previously published findings in a Caucasian sample.
Literature
1.
go back to reference Swanson JM, Flodman P, Kennedy J, Spence MA, Moyzis R, Schuck S, Murias M, Moriarity J, Barr C, Smith M, Posner M: Dopamine genes and ADHD. Neurosci Biobehav Rev. 2000, 24: 21-25. 10.1016/S0149-7634(99)00062-7.CrossRefPubMed Swanson JM, Flodman P, Kennedy J, Spence MA, Moyzis R, Schuck S, Murias M, Moriarity J, Barr C, Smith M, Posner M: Dopamine genes and ADHD. Neurosci Biobehav Rev. 2000, 24: 21-25. 10.1016/S0149-7634(99)00062-7.CrossRefPubMed
2.
go back to reference Asherson P, the IMAGE Consortium: Attention-deficit hyperactivity disorder in the post-genomic era. Eur Child Adolesc Psychiatry. 2004, 13: 50-70. 10.1007/s00787-004-1006-6.CrossRef Asherson P, the IMAGE Consortium: Attention-deficit hyperactivity disorder in the post-genomic era. Eur Child Adolesc Psychiatry. 2004, 13: 50-70. 10.1007/s00787-004-1006-6.CrossRef
3.
go back to reference Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA, Sklar P: Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005, 57: 1313-1323. 10.1016/j.biopsych.2004.11.024.CrossRefPubMed Faraone SV, Perlis RH, Doyle AE, Smoller JW, Goralnick JJ, Holmgren MA, Sklar P: Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiatry. 2005, 57: 1313-1323. 10.1016/j.biopsych.2004.11.024.CrossRefPubMed
5.
go back to reference Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R: Role of genotype in the cycle of violence in maltreated children. Science. 2002, 297: 851-854. 10.1126/science.1072290.CrossRefPubMed Caspi A, McClay J, Moffitt TE, Mill J, Martin J, Craig IW, Taylor A, Poulton R: Role of genotype in the cycle of violence in maltreated children. Science. 2002, 297: 851-854. 10.1126/science.1072290.CrossRefPubMed
6.
go back to reference Eklund J, Alm PO, af Klinteberg B: Monoamine oxidase activity and tri-iodothyronine level in violent offenders with early behavioural problems. Neuropsychobiology. 2005, 52 (3): 122-129. 10.1159/000087557.CrossRefPubMed Eklund J, Alm PO, af Klinteberg B: Monoamine oxidase activity and tri-iodothyronine level in violent offenders with early behavioural problems. Neuropsychobiology. 2005, 52 (3): 122-129. 10.1159/000087557.CrossRefPubMed
7.
go back to reference Shekim WO, Bylund DB, Alexson J, Glaser RD, Jones SB, Hodges K, Perdue S: Platelet MAO and measures of attention and impulsivity in boys with attention deficit disorder and hyperactivity. Psychiatry Res. 1986, 18: 179-188. 10.1016/0165-1781(86)90029-6.CrossRefPubMed Shekim WO, Bylund DB, Alexson J, Glaser RD, Jones SB, Hodges K, Perdue S: Platelet MAO and measures of attention and impulsivity in boys with attention deficit disorder and hyperactivity. Psychiatry Res. 1986, 18: 179-188. 10.1016/0165-1781(86)90029-6.CrossRefPubMed
8.
go back to reference Manuck SB, Flory JD, Ferrell RE, Mann JJ, Muldoon MF: A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity. Psychiatry Res. 2000, 95: 9-23. 10.1016/S0165-1781(00)00162-1.CrossRefPubMed Manuck SB, Flory JD, Ferrell RE, Mann JJ, Muldoon MF: A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity. Psychiatry Res. 2000, 95: 9-23. 10.1016/S0165-1781(00)00162-1.CrossRefPubMed
9.
go back to reference Lawson DC, Turic D, Langley K, Pay HM, Govan CF, Norton N, Hamshere ML, Owen MJ, O'Donovan MC, Thapar A: Association analysis of monoamine oxidase A and attention deficit hyperactivity disorder. Am J Med Genet. 2003, 116: 84-89. 10.1002/ajmg.b.10002.CrossRef Lawson DC, Turic D, Langley K, Pay HM, Govan CF, Norton N, Hamshere ML, Owen MJ, O'Donovan MC, Thapar A: Association analysis of monoamine oxidase A and attention deficit hyperactivity disorder. Am J Med Genet. 2003, 116: 84-89. 10.1002/ajmg.b.10002.CrossRef
10.
go back to reference Manor I, Tyano S, Mel E, Eisenberg J, Bachner-Melman R, Kotler M, Ebstein RP: Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): Preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuous performance test (TOVA). Mol Psychiatry. 2002, 7: 626-632. 10.1038/sj.mp.4001037.CrossRefPubMed Manor I, Tyano S, Mel E, Eisenberg J, Bachner-Melman R, Kotler M, Ebstein RP: Family-based and association studies of monoamine oxidase A and attention deficit hyperactivity disorder (ADHD): Preferential transmission of the long promoter-region repeat and its association with impaired performance on a continuous performance test (TOVA). Mol Psychiatry. 2002, 7: 626-632. 10.1038/sj.mp.4001037.CrossRefPubMed
11.
go back to reference Domschke K, Sheehan K, Lowe N, Kirley A, Mullins C, O'sullivan R, Freitag C, Becker T, Conroy J, Fitzgerald M, Gill M, Hawi Z: 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. Am J Med Genet B Neuropsychiatr Genet. 2005, 134B: 110-114. 10.1002/ajmg.b.30158.CrossRefPubMed Domschke K, Sheehan K, Lowe N, Kirley A, Mullins C, O'sullivan R, Freitag C, Becker T, Conroy J, Fitzgerald M, Gill M, Hawi Z: 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. Am J Med Genet B Neuropsychiatr Genet. 2005, 134B: 110-114. 10.1002/ajmg.b.30158.CrossRefPubMed
12.
go back to reference Hotamisligil GS, Breakefield XO: Human monoamine oxidase A gene determines levels of enzyme activity. Am J Hum Genet. 1991, 49: 383-392.PubMedPubMedCentral Hotamisligil GS, Breakefield XO: Human monoamine oxidase A gene determines levels of enzyme activity. Am J Hum Genet. 1991, 49: 383-392.PubMedPubMedCentral
13.
go back to reference Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moneci P, Williamson D, Ryan N: Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997, 36: 980-988. 10.1097/00004583-199707000-00021.CrossRefPubMed Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moneci P, Williamson D, Ryan N: Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry. 1997, 36: 980-988. 10.1097/00004583-199707000-00021.CrossRefPubMed
14.
go back to reference Conners CK: The Conners Rating Scales: Instruments for Assessments of Childhood Psychopathology. 1995, Duke University: Durham, USA Conners CK: The Conners Rating Scales: Instruments for Assessments of Childhood Psychopathology. 1995, Duke University: Durham, USA
15.
go back to reference Deckert J, Catalano M, Syagailo YV, Bosi M, Okladnova O, DiBella D, Noethen MM, Maffei P, Franke P, Fritze J, Maier W, Propping P, Beckmann H, Bellodi L, Lesch KP: Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder. Hum Mol Genet. 1999, 8: 621-624. 10.1093/hmg/8.4.621.CrossRefPubMed Deckert J, Catalano M, Syagailo YV, Bosi M, Okladnova O, DiBella D, Noethen MM, Maffei P, Franke P, Fritze J, Maier W, Propping P, Beckmann H, Bellodi L, Lesch KP: Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder. Hum Mol Genet. 1999, 8: 621-624. 10.1093/hmg/8.4.621.CrossRefPubMed
16.
go back to reference Dudbridge F: Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol. 2003, 25: 115-221. 10.1002/gepi.10252.CrossRefPubMed Dudbridge F: Pedigree disequilibrium tests for multilocus haplotypes. Genet Epidemiol. 2003, 25: 115-221. 10.1002/gepi.10252.CrossRefPubMed
Metadata
Title
Association study between the monoamine oxidase A gene and attention deficit hyperactivity disorder in Taiwanese samples
Authors
Xiaohui Xu
Keeley Brookes
Chih-Ken Chen
Yu-Shu Huang
Yu-Yu Wu
Philip Asherson
Publication date
01-12-2007
Publisher
BioMed Central
Published in
BMC Psychiatry / Issue 1/2007
Electronic ISSN: 1471-244X
DOI
https://doi.org/10.1186/1471-244X-7-10

Other articles of this Issue 1/2007

BMC Psychiatry 1/2007 Go to the issue