title: Polycyclic aromatic hydrocarbons are associated with insulin receptor substrate 2 methylation in adipose tissues of Korean women.
abstract: Polycyclic aromatic hydrocarbons (PAHs) are highly lipid soluble and are an increasing concern for general populations given their various adverse health effects, including obesity-related metabolic dysfunction. DNA methylation can act as a downstream effector for the biological effects of environmental exposures, but whether PAHs influence DNA methylation is unclear. To test for possible adverse effects of PAHs on adipose tissue (AT), we determined the promoter methylation status of 12 genes involved in glucose and lipid metabolism (CS, GLUT4, IR, IRS1, IRS2, LIPIN1, MCAD, PCK1, PCK2, PPARGC1Β, SDHA, and SREBP1) in visceral AT of Korean women by using methylation-specific PCR (MSP). IRS2 methylation alone was significantly associated with concentrations of individual PAH chemicals. When the PAH summary measure was used, the odds ratios of IRS2 hypermethylation across quartile of the PAH summary measure were 1, 1.7, 2.0, and 11.2 (95% confidence interval: 1.5-84.0) after adjusting for age and BMI (P trend=0.02). The strength of association between PAH summary measure and IRS2 hypermethylation was as similar as that of BMI. Collectively, these results suggested that lipophilic PAHs might be contributing factors to the pathogenesis of insulin resistance through methylation-mediated suppression of the IRS2 gene. However, further studies with large sample size are needed to confirm our findings.
authors.affiliation: Department of Anatomy and BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Young Hun
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Obstetrics and Gynecology, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Yoon Soon
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Preventive Medicine and BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 2-101 Dongin-dong, Jung-gu, Daegu 702-422, Republic of Korea. Electronic address: doskim@knu.ac.kr.
authors.forename: Duk Hee
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Anatomy and BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu, Republic of Korea. Electronic address: lee_dh@knu.ac.kr.
authors.forename: Dong Sun
authors.initials: DS
authors.lastname: Kim
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000328:Adult; D000368:Aged; D019175:DNA Methylation / Q000187:drug effects*; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011084:Polycyclic Aromatic Hydrocarbons / Q000633:toxicity*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D056910:Republic of Korea
chemical_list: D004785:Environmental Pollutants; C526297:IRS2 protein, human; D055504:Insulin Receptor Substrate Proteins; D011084:Polycyclic Aromatic Hydrocarbons
keywords: Adipose tissue; DNA methylation; Insulin receptor substrate 2; Methylation-specific PCR; Polycyclic aromatic hydrocarbons