Table 4. Significantly differentially methylated CpG sites by per- and poly-fluoroalkyl substances exposure among key hypothesis-driven genes (p < 0.0025).
| PFASs with significant association | Probe ID | Gene name | Locus | Genic feature | Average DNA methylation at CpG site (%) | Effect estimate (SE)† | p-value |
|---|---|---|---|---|---|---|---|
| PFHxS | cg10457648 | NR1I2 | chr3:119497980 | Near TSS | 87.9 | 0.007 (0.002) | 0.0018 |
| cg06491638 | HMGCS1 | chr5:43288815 | 3′ UTR | 88.6 | 0.007 (0.002) | 0.0014 | |
| cg19699994 | ABCA1 | chr9:107554439 | Gene body | 84.9 | 0.017 (0.006) | 0.0023 | |
| n-PFOA | cg23519812 | ACOT2 | chr14:74036744 | Gene body; south shore | 20.0 | -0.026 (0.008) | 0.0008 |
| Sb-PFOA | cg21946299 | PPARG | chr3:12329166 | Near TSS; CpG island | 2.9 | 0.005 (0.002) | 0.0009 |
| cg20293950 | CD36 | chr7:80273190 | 5′ UTR | 73.9 | 0.028 (0.009) | 0.0017 | |
| PFNA | cg23236365 | ABCA1 | chr9:107618721 | Gene body | 83.4 | 0.012 (0.004) | 0.0018 |
| PFUnDA | cg13369760 | PPARG | chr3:12446442 | Gene body | 93.9 | -0.006 (0.001) | 0.0000 |
| cg04029738 | FASN | chr17:80049290 | Gene body; CpG island | 94.7 | 0.006 (0.002) | 0.0024 |
Effect estimates represent the proportion of methylation change per ln-transformed unit of PFASs (ng/ml for PFHxS, n-PFOA and PFNA) or the difference when comparing participants with detectable versus nondetectable concentrations (for categorical PFASs: Sb-PFOA and PFUnDA). Models adjust for age, gender, race (white vs all other), ethnicity (Hispanic and non-Hispanic), PC1, PC2, PC3, neutrophils, plasmablasts, CD8+ naive T cells and CD8+CD28-CD45RA- cells. In total 433 CpG sites from 20 genes were selected based on differential expression after acute treatment to multiple PFASs in cultured human hepatocytes. Results are shown here for PFASs – DNA methylation relationships at loci with p < 0.0025 (0.05/20 genes).
chr: Chromosome; PFAS: Per- and poly-fluoroalkyl substance; PFHxS: Perfluorohexane sulfonate; PFNA: Perfluorononanoate; PFUnDA: Perfluoroundecanoate; n-PFOA: Linear perfluorooctanoate; Sb-PFOA: Sum of branched PFOA isomer; SE: Standard error; TSS: Transcription start site; UTR: Untranslated region.