Pesticides and chemical exposures, DNA methylation, and SLE phenotypes

Genetic, epigenetic and environmental risk factors have been implicated in the pathogenesis of SLE. Environmental exposures can influence DNA methylation. We have completed genome-wide methylation profiling for a large group of SLE patients and demonstrated significant differences in methylation profiles according to autoantibody status and renal involvement. These differences may represent a link between environmental exposures and SLE manifestations. Very few studies have measured exposures in biological samples of SLE patients. The overall goals of this study are to examine the association of chemical exposures with disease phenotype and DNA methylation patterns in SLE. We will characterize serum levels of environmental organic acids (EOAs) in 400 SLE patients with well characterized disease, including clinical and serologic outcomes; socioeconomic data; as well as genome-wide genetic and DNA methylation profiles. Banked serum will be analyzed by a non-targeted approach with liquid chromatography-quadrupole time of flight mass spectrometry (LC-QTOF/MS). This technology allows for the analysis of hundreds of chemicals in an unbiased manner. We will then determine whether exposure to EOAs is associated with disease phenotype and/or DNA methylation profiles in SLE. This will be the first study assessing environmental exposures, DNA methylation and disease phenotypes in a large cohort of SLE patients.