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PMID: 16483362 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

The quantification of COMT mRNA in post mortem cerebellum tissue: diagnosis, genotype, methylation and expression.

BMC medical genetics ·Vol. 7 ·2006-02-16 ·Pages 10

Dempster EL, Mill J, Craig IW, Collier DA

Abstract

The COMT gene is located on chromosome 22q11, a region strongly implicated in the aetiology of several psychiatric disorders, in particular schizophrenia. Previous research has suggested that activity and expression of COMT is altered in schizophrenia, and is mediated by one or more polymorphisms within the gene, including the functional Val158Met polymorphism. In this study we examined the expression levels of COMT mRNA using quantitative RT-PCR in 60 post mortem cerebellum samples derived from individuals with schizophrenia, bipolar disorder, depression, and no history of psychopathology. Furthermore, we have examined the methylation status of two CpG sites in the promoter region of the gene. We found no evidence of altered COMT expression or methylation in any of the psychiatric diagnoses examined. We did, however, find evidence to suggest that genotype is related to COMT gene expression, replicating the findings of two previous studies. Specifically, val158met (rs165688; Val allele) rs737865 (G allele) and rs165599 (G allele) all showed reduced expression (P < 0.05). Finally, we observe a strong sexual dimorphism in COMT expression, with females exhibiting significantly greater levels of COMT mRNA. The expression of COMT does not appear to be altered in the cerebellum of individuals suffering from schizophrenia, bipolar disorder or depression, but does appear to be influenced by single nucleotide polymorphisms within the gene.

MeSH Terms
Bipolar Disorder/diagnosis,genetics,pathology Catechol O-Methyltransferase/genetics,metabolism Cerebellum/metabolism,pathology DNA Methylation Depressive Disorder/diagnosis,genetics,pathology Female Gene Expression Genetic Predisposition to Disease Genotype Humans Male Mental Disorders/genetics Polymorphism, Single Nucleotide RNA, Messenger/metabolism Schizophrenia/diagnosis,genetics,pathology Sex Characteristics
Chemicals
RNA, Messenger Catechol O-Methyltransferase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Dempster Emma L
Molecular Genetics, Psychological Medicine, Institute of Psychiatry, London, UK. [email protected]
Mill Jonathan
Craig Ian W
Collier David A
References (37)
37 references, click to expand
  1. Human catechol-O-methyltransferase pharmacogenetics: description of a functional polymorphism and its potential application to neuropsychiatric disorders.
    Pharmacogenetics. 1996 Jun;6(3):243-50 PMID: 8807664
  2. Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme.
    Biochemistry. 1995 Apr 4;34(13):4202-10 PMID: 7703232
  3. A modified and improved method for bisulphite based cytosine methylation analysis.
    Nucleic Acids Res. 1996 Dec 15;24(24):5064-6 PMID: 9016686
  4. Genotype determining low catechol-O-methyltransferase activity as a risk factor for obsessive-compulsive disorder.
    Proc Natl Acad Sci U S A. 1997 Apr 29;94(9):4572-5 PMID: 9114031
  5. Catechol-O-methyltransferase polymorphisms and schizophrenia: a transmission disequilibrium study in multiply affected families.
    Psychiatr Genet. 1997 Autumn;7(3):97-101 PMID: 9323320
  6. Association study of a functional catechol-O-methyltransferase gene polymorphism in Japanese schizophrenics.
    Neurosci Lett. 1998 Feb 27;243(1-3):109-12 PMID: 9535125
  7. Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior.
    Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9991-6 PMID: 9707588
  8. Methylation pharmacogenetics: catechol O-methyltransferase, thiopurine methyltransferase, and histamine N-methyltransferase.
    Annu Rev Pharmacol Toxicol. 1999;39:19-52 PMID: 10331075
  9. Family-based association studies support a sexually dimorphic effect of COMT and MAOA on genetic susceptibility to obsessive-compulsive disorder.
    Biol Psychiatry. 1999 May 1;45(9):1178-89 PMID: 10331110
  10. Linkage disequilibrium on the COMT gene in French schizophrenics and controls.
    Am J Med Genet. 1999 Oct 15;88(5):452-7 PMID: 10490696
  11. Differential expression of human COMT alleles in brain and lymphoblasts detected by RT-coupled 5' nuclease assay.
    Psychopharmacology (Berl). 2004 Dec;177(1-2):178-84 PMID: 15290009
  12. Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: a large-scale association study plus meta-analysis.
    Biol Psychiatry. 2005 Jan 15;57(2):139-44 PMID: 15652872
  13. Site-specific cytosine methylation in S-COMT promoter in 31 brain regions with implications for studies involving schizophrenia.
    Am J Med Genet B Neuropsychiatr Genet. 2005 Feb 5;133B(1):37-42 PMID: 15635661
  14. Haplotypic association spanning the 22q11.21 genes COMT and ARVCF with schizophrenia.
    Mol Psychiatry. 2005 Apr;10(4):353-65 PMID: 15340358
  15. Moderation of the effect of adolescent-onset cannabis use on adult psychosis by a functional polymorphism in the catechol-O-methyltransferase gene: longitudinal evidence of a gene X environment interaction.
    Biol Psychiatry. 2005 May 15;57(10):1117-27 PMID: 15866551
  16. Separate and interacting effects within the catechol-O-methyltransferase (COMT) are associated with schizophrenia.
    Mol Psychiatry. 2005 Jun;10(6):589-97 PMID: 15505638
  17. Catechol-O-methyltransferase (COMT): biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors.
    Pharmacol Rev. 1999 Dec;51(4):593-628 PMID: 10581325
  18. Family-based linkage disequilibrium mapping using SNP marker haplotypes: application to a potential locus for schizophrenia at chromosome 22q11.
    Mol Psychiatry. 2000 Jan;5(1):77-84 PMID: 10673772
  19. The stanley foundation brain collection and neuropathology consortium.
    Schizophr Res. 2000 Aug 3;44(2):151-5 PMID: 10913747
  20. Human morbid genetics revisited: relevance of epigenetics.
    Trends Genet. 2001 Mar;17(3):142-6 PMID: 11226607
  21. Dopamine transporter immunoreactivity in monkey cerebral cortex: regional, laminar, and ultrastructural localization.
    J Comp Neurol. 2001 Mar 26;432(1):119-36 PMID: 11241381
  22. Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia.
    Proc Natl Acad Sci U S A. 2001 Jun 5;98(12):6917-22 PMID: 11381111
  23. Dopamine uptake through the norepinephrine transporter in brain regions with low levels of the dopamine transporter: evidence from knock-out mouse lines.
    J Neurosci. 2002 Jan 15;22(2):389-95 PMID: 11784783
  24. A functional polymorphism in the COMT gene and performance on a test of prefrontal cognition.
    Am J Psychiatry. 2002 Apr;159(4):652-4 PMID: 11925305
  25. Effects of catecholamine uptake blockers in the caudate-putamen and subregions of the medial prefrontal cortex of the rat.
    Brain Res. 2002 May 17;936(1-2):58-67 PMID: 11988230
  26. Catechol-O-methyltransferase Val-108/158-Met gene variants associated with performance on the Wisconsin Card Sorting Test.
    Arch Gen Psychiatry. 2002 Jul;59(7):662-3 PMID: 12090821
  27. A highly significant association between a COMT haplotype and schizophrenia.
    Am J Hum Genet. 2002 Dec;71(6):1296-302 PMID: 12402217
  28. Association between a functional catechol O-methyltransferase gene polymorphism and schizophrenia: meta-analysis of case-control and family-based studies.
    Am J Psychiatry. 2003 Mar;160(3):469-76 PMID: 12611827
  29. A haplotype implicated in schizophrenia susceptibility is associated with reduced COMT expression in human brain.
    Am J Hum Genet. 2003 Jul;73(1):152-61 PMID: 12802784
  30. The role of catechol-O-methyltransferase in the inactivation of catecholestrogen.
    Cell Mol Neurobiol. 2003 Jun;23(3):289-91 PMID: 12825827
  31. Catechol O-methyltransferase (COMT) mRNA expression in the dorsolateral prefrontal cortex of patients with schizophrenia.
    Neuropsychopharmacology. 2003 Aug;28(8):1521-30 PMID: 12799619
  32. Recent advances in the genetics of schizophrenia.
    Hum Mol Genet. 2003 Oct 15;12 Spec No 2:R125-33 PMID: 12952866
  33. Catechol-o-methyltransferase (COMT) and proline dehydrogenase (PRODH) mRNAs in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and major depression.
    Synapse. 2004 Feb;51(2):112-8 PMID: 14618678
  34. The origin of schizophrenia: genetic thesis, epigenetic antithesis, and resolving synthesis.
    Biol Psychiatry. 2004 May 15;55(10):965-70 PMID: 15121478
  35. COMT haplotypes suggest P2 promoter region relevance for schizophrenia.
    Mol Psychiatry. 2004 Sep;9(9):859-70 PMID: 15098000
  36. Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain.
    Am J Hum Genet. 2004 Nov;75(5):807-21 PMID: 15457404
  37. Preferential transmission of the high activity allele of COMT in schizophrenia.
    Psychiatr Genet. 1996 Fall;6(3):131-3 PMID: 8902889
Article Info
Journal
BMC medical genetics
Abbr.
BMC Med Genet
ISSN
1471-2350
DOI
10.1186/1471-2350-7-10
Email
[email protected]
Published
2006-02-16
Epub
2006-00-16
Pages
10
Language
English
Region
England
NLM ID
100968552
PMCID
PMC1456954
Subset
IM
External Links
PubMed source DOI: 10.1186/1471-2350-7-10 PMC Full Text View journal details
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