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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Molecular Genetics, Psychological Medicine, Institute of Psychiatry, London, UK. e.dempster@iop.kcl.ac.uk
Emma L
EL
Dempster
Jonathan
J
Mill
Ian W
IW
Craig
David A
DA
Collier
D001714:Bipolar Disorder / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D002394:Catechol O-Methyltransferase / Q000235:genetics* / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism* / Q000473:pathology; D019175:DNA Methylation; D003866:Depressive Disorder / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D005260:Female; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000378:metabolism; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D012727:Sex Characteristics
D012333:RNA, Messenger; D002394:Catechol O-Methyltransferase