Relationships of Ambient Fine Particle Air Pollution, Endothelial Function, and Blood DNA Methylation Age:Implications for Renal Health

摘要

Background: Research has demonstrated associations of long-term ambient fine particulate matter (PM_(2.5)) with renal function and DNA methylation (DNAm) age, an epigenome-wide DNA methylation-based predictor of chronological age. It has also been shown that the association of PM_(2.5) component species with DNAm-age can be modified by normal variation of genes involved in endothelial physiology. Objective: Given that renal and endothelial physiology are closely related, we determined the relationship of DNAm-age with measures of renal function and examined the modifying role of DNAm-age on the relationship of PM_(2.5) with renal function. Methods: This analysis included 559 participants from the Normative Aging Study with multiple visits between 2000 and 2011 (n=943 visits). We estimated one-year PM_(2.5)and component species (ammonium and sulfate) levels at participants' addresses using the GEOS-chem model. Participants' blood, collected at each study visit, was used to derive DNAm-age and four renal function markers (serum creatinine, serum BUN, eGFR, and BUN-to-creatinine ratio). Blood DNAm-age was calculated using CpG sites on the lllumina HumanMethylation450 BeadChip. We estimated associations of DNAm-age with renal function using linear mixed-effects models adjusted for chronological age, lifestyle/environmental factors, and aging-related diseases. Results: A one-year increase in DNAm-age was positively associated with serum creatinine (β = 0.006; 95%Cl 0.001, 0.010). DNAm-age was negatively associated with both eGFR (β = -0.34 mL/min/1.73 m~2; 95%Cl -0.51, -0.18) and BUN-to-creatinine ratio (β = -0.07; 95%Cl -0.13, -0.02). The data also suggested a modifying effect of DNAm-age on the association of one-year PM_(2.5) and Ammonium levels with eGFR. Conclusions: DNAm-age is significantly associated with measures of renal function. Additional work is necessary to understand these relationships particularly in the contexts of PM_(2.5) exposure, effect modification, and mediation.