Metabolites Associated With Per- and Polyfluoroalkyl Substance (PFAS) Levels in an Ethnically Diverse Underserved At-Risk Rural Population
By Jawan W Abdulrahim, Heather M Stapleton, Maggie Nguyen, Lydia C Kwee, Olga Ilkayeva, Cherry M Beasley, John W Stanifer, and Svati H Shah
Circulation
November 25, 2019
Per- and polyfluoroalkyl substances (PFASs) are manufactured compounds used in a number of consumer products and have been linked to several health conditions. In North Carolina (NC), vulnerable populations may have higher PFAS exposure related to contamination from nearby chemical plants. We sought to determine PFAS exposure and explore potential biological pathways affected using metabolomic profiling.
Methods: The sample consisted of 50 underserved individuals that reside in Robeson County, NC, where PFAS contamination has been implicated. Tandem flow injection mass spectrometry (MS)-based targeted and gas chromatography (GC-MS) based non-targeted metabolomic profiling, as well as liquid chromatography-MS methods to measure 11 PFASs, were performed on frozen serum samples. PFASs and metabolites with >25% values below lower limits of quantification were treated as binary variables (detected/undetected); those with <50% missing values were treated as quantitative variables. We tested the association between PFAS and metabolite levels using Spearman correlation, Wilcoxon rank sum, or Fisher’s exact test, as appropriate.
Results: We analyzed a total of 165 metabolites (60 targeted, 105 nontargeted) and seven PFASs. Four PFASs were excluded due to low level of detection. Overall, 1485 PFAS-metabolite tests were performed and 71 (4.8%) were statistically significant (nominal p<0.05). Our most significant targeted metabolite results were for perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), where we found correlations between alanine (rho -0.4, p=0.004) and C20:4 long chain acylcarnitine (LCAC) (rho 0.4, p=0.004), respectively. The metabolite correlated with the greatest number of PFASs was alanine (p=0.004-0.02). We also found correlations between C18-OH/C16-DC LCAC with PFBA (rho -0.3, p=0.02); and C14:1 (rho -0.3 p=0.021) and C20:4 (rho 0.3 p=0.018) LCAC with perfluorohexanesulfonic acid (PFHxS).
Conclusions: We found evidence of serum metabolites that reflect mitochondrial dysfunction correlated with PFAS levels in an at-risk population. These metabolites have previously been associated with adverse cardiovascular outcomes and may highlight potential mechanisms by which PFASs exert toxicity.
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