Polycyclic aromatic hydrocarbons are associated with insulin receptor substrate 2 methylation in adipose tissues of Korean women

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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, PPARGC1B, 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.

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