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

다국어 초록 (Multilingual Abstract)

<P><B>Abstract</B></P> <P>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 (<I>CS, GLUT4, IR, IRS1, IRS2, LIPIN1, MCAD, PCK1, PCK2, PPARGC1</I>Β<I>, SDHA,</I> and <I>SREBP1</I>) in visceral AT of Korean women by using methylation-specific PCR (MSP). <I>IRS2</I> methylation alone was significantly associated with concentrations of individual PAH chemicals. When the PAH summary measure was used, the odds ratios of <I>IRS2</I> 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 <I>IRS2</I> 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 <I>IRS2</I> gene. However, further studies with large sample size are needed to confirm our findings.</P> <P><B>Highlights</B></P> <P> <UL> <LI> <I>IRS2</I> methylation was associated with concentrations of individual PAH chemicals. </LI> <LI> The association strength of PAH summary measure was similar to that of BMI. </LI> <LI> IRS2 promoter was methylated in 60.4% (32/53) of visceral adipose tissue. </LI> </UL> </P>