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The influence of metabolic syndrome, physical activity and genotype on catechol-O-methyl transferase promoter-region methylation in schizophrenia

The Pharmacogenomics Journal volume 13, pages 264–271 (2013)Cite this article

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Abstract

The catechol-O-methyl transferase (COMT) 158Val/Met variant has been suggested to play a role in COMT function. Epigenetic regulation of COMT may further influence the prevalence of metabolic syndrome in these patient populations. This study examined the correlation between COMT promoter methylation and metabolic syndrome in schizophrenia patients receiving atypical antipsychotic (AAP) therapy. DNA was extracted from peripheral blood samples of schizophrenia subjects screened for metabolic syndrome. Pyrosequencing was used to analyze two methylation sites of the soluble COMT (COMT-s) promoter region. Associations between AAP use, lifestyle variables, metabolic syndrome and COMT genotype with peak methylation values were analyzed. Data are reported in 85 subjects. Methylation on CpG site 1 had a mean of 79.08% (±4.71) and it was 12.43% (±1.19) on site 2. COMT genotype proved to be an indicator of COMT methylation status on site 1 (F(2, 84)=5.78, P=0.0044) and site 2 (F(2, 84),=3.79, P=0.027). A significant negative correlation between physical activity and COMT promoter region methylation was found in Val/Val homozygous patients (site 1: P=0.013 and site 2: P=0.019). Those homozygous for Met/Met showed a positive correlation between promoter site methylation and physical activity (site 1: P=0.027, site 2: P=0.005), and between CpG site methylation and metabolic syndrome (site 1: P=0.002; site 2: P=0.001). The results of this study suggest that COMT promoter region methylation is largely influenced by COMT genotype and that physical activity plays a significant role in epigenetic modulation of COMT.

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Acknowledgements

We acknowledge the subjects who participated in this research, the Washtenaw Community Health Organization (WCHO) and the Detroit-Wayne County Community Mental Health Agency (D-WCCMHA). Last, we acknowledge Dr Richard Pilsner who provided guidance with the methylation assay. The following funding sources were utilized for this publication: NIMH (R01 MH082784) and the NIH-NCCR for the Michigan Institute for Clinical and Health Research (MICHR UL1RR024986) and the Chemistry Core of the Michigan Diabetes Research and Training Center (NIH5P60 DK 20572).

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Authors and Affiliations

  1. Department of Clinical Social and Administrative Sciences, University of Michigan College of Pharmacy, Ann Arbor, MI, USA

    S A Lott, K J Burghardt, M J Bly, T B Grove & V L Ellingrod

  2. Department of Psychiatry, University of Michigan School of Medicine, Ann Arbor, MI, USA

    P R Burghardt, T B Grove & V L Ellingrod

  3. The Molecular & Behavioral Neuroscience Institute (MBNI), University of Michigan, Ann Arbor, MI, USA

    P R Burghardt

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  1. S A Lott
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Correspondence to V L Ellingrod.

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Lott, S., Burghardt, P., Burghardt, K. et al. The influence of metabolic syndrome, physical activity and genotype on catechol-O-methyl transferase promoter-region methylation in schizophrenia. Pharmacogenomics J 13, 264–271 (2013). https://doi.org/10.1038/tpj.2012.6

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