Skip to main content

Advertisement

Log in

Meta-analysis of Association Between a Catechol-O-Methyltransferase Gene Polymorphism and Attention Deficit Hyperactivity Disorder

  • ORIGINAL PAPER
  • Published:
Behavior Genetics Aims and scope Submit manuscript

Abstract

There have been conflicting reports on the association between the Val158/108Met polymorphism of the catechol-O-methyltransferase (COMT) gene and attention deficit hyperactivity disorder (ADHD). Therefore we would like to perform a meta-analysis of previous studies to assess the overall magnitude and significance of the association. Family-based and case–control studies of the association between the COMT gene polymorphism and ADHD were searched systematically and comprehensively. Odds ratios (OR) of association were pooled by the fixed effects model if no significant heterogeneity was present among different studies. Subgroup analysis by gender and ADHD subtypes were also performed. Eleven family-based and two case–control studies were identified. After pooling the results, no significant association between the COMT Val158/108Met polymorphism and ADHD was found (OR 0.99 (95% CI: 0.88–1.12), P = 0.87). There was also no significant association when the results were stratified by gender or ADHD subtype. There was no significant statistical heterogeneity (χ2 = 12.27, P = 0.2) although clinical heterogeneity was present in the studies, especially the ethnicity of subjects. Sensitivity analysis demonstrated absence of undue influence of any single study. Standard regression analysis showed no significant publication bias. We concluded that no significant association was present between the most common COMT gene polymorphism and ADHD. Further studies should employ larger sample size in more homogeneous subjects. Further investigations in moderator variables and gene–gene and gene–environment interactions are also warranted.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders: DSM-IV, 4th edn. American Psychiatric Association, Washington DC

    Google Scholar 

  • Barr CL, Wigg K, Malone M et al (1999) Linkage study of catechol-O-methyltransferase and attention-deficit hyperactivity disorder. Am J Med Genet 88:710–713

    Article  PubMed  CAS  Google Scholar 

  • Bellgrove MA, Domschke K, Hawi Z et al (2005) The methionine allele of the COMT polymorphism impairs prefrontal cognition in children and adolescents with ADHD. Exp Brain Res 163:352–360

    Article  PubMed  CAS  Google Scholar 

  • Benjamin J, Osher Y, Kotler M et al (2000) Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: dopamine receptor D4 (DRD4), serotonin transporter promoter region (5-HTTLPR) and catechol-O-methyltransferase (COMT). Mol Psychiat 5:96–100

    Article  CAS  Google Scholar 

  • Bertocci B, Miggiano V, Da Prada M et al (1991) Human catechol-O-methyltransferase: cloning and expression of the membrane-associated form. Proc Natl Acad Sci USA 88:1416–1420

    Article  PubMed  CAS  Google Scholar 

  • Biederman J, Faraone SV (2005) Attention-deficit hyperactivity disorder. Lancet 366:237–248

    Article  PubMed  Google Scholar 

  • Egger M, Davey Smith G, Schneider M et al (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    PubMed  CAS  Google Scholar 

  • Egger M, Smith GD (2001) Principles of and procedures for systematic reviews. In: Egger M, Smith GD, Altman DG (eds) Systematic reviews in health care: meta-analysis in context. BMJ Publishing Group, London, pp 23–42

    Chapter  Google Scholar 

  • Eisenberg J, Mei-Tal G, Steinberg A et al (1999). Haplotype relative risk study of catechol-O-methyltransferase (COMT) and attention deficit hyperactivity disorder (ADHD): association of the high-enzyme activity Val allele with ADHD impulsive-hyperactive phenotype. Am J Med Genet 88:497–502

    Article  PubMed  CAS  Google Scholar 

  • Ernst M, Liebenauer LL, King AC et al (1994) Reduced brain metabolism in hyperactive girls. J Am Acad Child Adolesc Psychiatry 33:858–868

    Article  CAS  Google Scholar 

  • Faraone SV, Doyle AE, Mick E et al (2001) Meta-analysis of the association between the 7-repeat allele of the dopamine D(4) receptor gene and attention deficit hyperactivity disorder. Am J Psychiat 158:1052–1057

    Article  PubMed  CAS  Google Scholar 

  • Faraone SV, Perlis RH, Doyle AE et al (2005) Molecular genetics of attention-deficit/hyperactivity disorder. Biol Psychiat 57:1313–1323

    Article  PubMed  CAS  Google Scholar 

  • Faraone SV, Sergeant J, Gillberg C et al (2003) The worldwide prevalence of ADHD: is it an American condition? World Psychiat 2:104–113

    Google Scholar 

  • Gogos JA, Morgan M, Luine V et al (1998) Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior. Proc Natl Acad Sci USA 95:9991–9996

    Article  PubMed  CAS  Google Scholar 

  • Goldman-Rakic PS (1998) The cortical dopamine system: role in memory and cognition. Adv Pharmacol 42:707–711

    Article  PubMed  CAS  Google Scholar 

  • Grossman MH, Emanuel BS, Budarf ML (1992) Chromosomal mapping of the human catechol-O-methyltransferase gene to 22q11.1–q11.2. Genomics 12:822–825

    Article  PubMed  CAS  Google Scholar 

  • Hawi Z, Millar N, Daly G et al (2000) No association between catechol-O-methyltransferase (COMT) gene polymorphism and attention deficit hyperactivity disorder (ADHD) in an Irish sample. Am J Med Genet 96:282–284

    Article  PubMed  CAS  Google Scholar 

  • Jiang SD, Wu XD, Zhang Y et al (2005) No association between attention-deficit hyperactivity disorder and catechol-O-methyltransferase gene in Chinese. Yi Chuan Xue Bao 32:784–788

    PubMed  CAS  Google Scholar 

  • Lachman HM, Morrow B, Shprintzen R et al (1996) Association of codon 108/158 catechol-O-methyltransferase gene polymorphism with the psychiatric manifestations of velo-cardio-facial syndrome. Am J Med Genet 67:468–472

    Article  PubMed  CAS  Google Scholar 

  • Maher BS, Marazita ML, Ferrell RE et al (2002) Dopamine system genes and attention deficit hyperactivity disorder: a meta-analysis. Psychiat Genet 12:207–215

    Article  Google Scholar 

  • Manor I, Kotler M, Sever Y et al (2000) Failure to replicate an association between the catechol-O-methyltransferase polymorphism and attention deficit hyperactivity disorder in a second, independently recruited Israeli cohort. Am J Med Genet 96:858–860

    Article  PubMed  CAS  Google Scholar 

  • McLeod HL, Syvanen AC, Githang’a J et al (1998) Ethnic differences in catechol-O-methyltransferase pharmacogenetics: frequency of the codon 108/158 low activity allele is lower in Kenyan than Caucasian or south-west Asian individuals. Pharmacogenetics 8:195–199

    PubMed  CAS  Google Scholar 

  • Ovtscharoff W, Eusterschulte B, Zienecker R et al (1992) Sex differences in densities of dopaminergic fibers and GABAergic neurons in the prenatal rat striatum. J Comp Neurol 323:299–304

    Article  PubMed  CAS  Google Scholar 

  • Palmatier MA, Kang AM, Kidd KK (1999) Global variation in the frequencies of functionally different catechol-O-methyltransferase alleles. Biol Psychiat 46:557–567

    Article  PubMed  CAS  Google Scholar 

  • Payton A, Holmes J, Barrett JH et al (2001) Examining for association between candidate gene polymorphisms in the dopamine pathway and attention-deficit hyperactivity disorder: a family-based study. Am J Med Genet 105:464–470

    Article  PubMed  CAS  Google Scholar 

  • Purper-Ouakil D, Wohl M, Mouren MC et al (2005) Meta-analysis of family-based association studies between the dopamine transporter gene and attention deficit hyperactivity disorder. Psychiat Genet 15:53–59

    Article  CAS  Google Scholar 

  • Qian Q, Wang Y, Zhou R et al (2003) Family-based and case–control association studies of catechol-O-methyltransferase in attention deficit hyperactivity disorder suggest genetic sexual dimorphism. Am J Med Genet B Neuropsychiat Genet 118:103–109

    Article  Google Scholar 

  • Sergeant JA, Geurts H, Oosterlaan J (2002) How specific is a deficit of executive functioning for attention-deficit/hyperactivity disorder? Behav Brain Res 130:3–28

    Article  PubMed  Google Scholar 

  • Taerk E, Grizenko N, Ben Amor L et al (2004) Catechol-O-methyltransferase (COMT) Val108/158 Met polymorphism does not modulate executive function in children with ADHD. BMC Med Genet 5:30

    Article  PubMed  Google Scholar 

  • Tahir E, Curran S, Yazgan Y et al (2000) No association between low- and high-activity catecholamine-O-methyltransferase (COMT) and attention deficit hyperactivity disorder (ADHD) in a sample of Turkish children. Am J Med Genet 96:285–288

    Article  PubMed  CAS  Google Scholar 

  • Tenhunen J, Salminen M, Lundstrom K et al (1994) Genomic organization of the human catechol-O-methyltransferase gene and its expression from two distinct promoters. Eur J Biochem 223:1049–1059

    Article  PubMed  CAS  Google Scholar 

  • Turic D, Williams H, Langley K et al (2005) A family based study of catechol-O-methyltransferase (COMT) and attention deficit hyperactivity disorder (ADHD). Am J Med Genet B Neuropsychiat Genet 133:64–67

    Article  Google Scholar 

  • Vandenbergh DJ, Rodriguez LA, Miller IT et al (1997) High-activity catechol-O-methyltransferase allele is more prevalent in polysubstance abusers. Am J Med Genet 74:439–442

    Article  PubMed  CAS  Google Scholar 

  • Zhang XN, Ruan LM, Le YP et al (2003) Association analysis between attention-deficit hyperactivity disorder and Val158Met polymorphism of catechol-O-methyltransferase gene. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 20:322–324

    PubMed  Google Scholar 

Download references

Acknowledgments

We are grateful to Mr. Wilfred Wong for providing statistical advice in this meta-analysis.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Daniel Ka Leung Cheuk.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Cheuk, D.K.L., Wong, V. Meta-analysis of Association Between a Catechol-O-Methyltransferase Gene Polymorphism and Attention Deficit Hyperactivity Disorder. Behav Genet 36, 651–659 (2006). https://doi.org/10.1007/s10519-006-9076-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10519-006-9076-5

Keywords

Navigation