title: Metabolic syndrome components are associated with DNA hypomethylation.
abstract: BACKGROUND
  Disturbances of DNA methylation have been associated with multiple diseases, including cardiovascular disease, cancer and, as some have suggested, glucometabolic disturbances. Our aim was to assess the association of the metabolic syndrome and its individual components with DNA methylation in a population-based study.
  
  
  METHODS
  In a human population (n = 738) stratified by age, sex and glucose metabolism, we explored associations of the metabolic syndrome according to National Cholesterol Education Program/Adult Treatment Panel-III criteria and its individual components (fasting glucose, high-density lipoprotein cholesterol, triglycerides, blood pressure, waist circumference) with global leukocyte DNA methylation. DNA methylation was measured as the methylcytosine/cytosine ratio in peripheral leukocytes using liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  Individuals with the metabolic syndrome had relative DNA hypomethylation compared to participants without the syndrome (β = -0.05; p = 0.01). This association was mainly attributable to linear associations of two metabolic syndrome components with DNA methylation: fasting plasma glucose (β = -0.02; p = 0.004) and high-density lipoprotein cholesterol (β = 0.07; p = 0.004). People with type 2 diabetes or impaired glucose metabolism had DNA hypomethylation compared to normoglycemic individuals (β = -0.05; p = 0.004).
  
  
  CONCLUSIONS
  DNA hypomethylation is independently associated with hyperglycemia and low high-density lipoprotein cholesterol, both essential components of the metabolic syndrome. The potential implications and direction of possible causality require further study.
authors: Faculty of Medicine, VU University Medical Center, Amsterdam, The Netherlands.
authors: Roosmarijn
authors: R
authors: Luttmer
authors: Center for Prevention and Health Services Research, National Institute of Public Health and the Environment, Bilthoven, The Netherlands.
authors: Annemieke M
authors: AM
authors: Spijkerman
authors: Department of Clinical Chemistry and Institute for Cardiovascular Research ICaR-VU, VU University Medical Center, Amsterdam, The Netherlands.
authors: Robert M
authors: RM
authors: Kok
authors: Department of Clinical Chemistry and Institute for Cardiovascular Research ICaR-VU, VU University Medical Center, Amsterdam, The Netherlands.
authors: Carel
authors: C
authors: Jakobs
authors: Department of Clinical Chemistry and Institute for Cardiovascular Research ICaR-VU, VU University Medical Center, Amsterdam, The Netherlands.
authors: Henk J
authors: HJ
authors: Blom
authors: Department of Internal Medicine and Institute for Cardiovascular Research ICaR-VU, VU University Medical Center, The Netherlands.
authors: Erik H
authors: EH
authors: Serne
authors: Institute for Research in Extramural Medicine (EMGO Institute), VU University Medical Centre, Amsterdam, The Netherlands.
authors: Jacqueline M
authors: JM
authors: Dekker
authors: Department of Internal Medicine and Institute for Cardiovascular Research ICaR-VU, VU University Medical Center, The Netherlands. Electronic address:y.smulders@vumc.nl.
authors: Yvo M
authors: YM
authors: Smulders
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D004247:DNA / Q000378:metabolism*; D019175:DNA Methylation; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005215:Fasting; D005260:Female; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000235:genetics / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference
chemical_list: D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D004247:DNA; D002784:Cholesterol