Association of Global DNA Methylation and Global DNA Hydroxymethylation with Metals and Other Exposures in Human Blood DNA Samples

http://dx.doi.org/10.1289/ehp.1306674



Table 2. Cross-sectional associations [OR (95% CI)] of global DNA methylation (%5-mC) and global DNA hydroxymethylation (%5-hmC) in 1989–1991 (visit 1) by participant characteristics in the Strong Heart Study (SHS).
Characteristic n Methylation Hydroxymethylation
Model 1 Model 2 Model 1 Model 2
Abbreviations: NA, not available; Ref, referent. Model 1 was unadjusted; model 2 was adjusted for age (years), sex, smoking status (never, former, current), and BMI (kg/m2).
aSex-specific medians for waist circumference were 130 cm in men and 130 cm in women. bSex-specific medians for percent body fat were 29.8% in men and 41.40% in women. cSum of inorganic and methylated arsenic species in urine.
Age (years)          
< 54 24 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 54 24 0.79 (0.48, 1.30) 0.78 (0.46, 1.32) 0.76 (0.46, 1.26) 0.90 (0.54, 1.50)
Sex          
Male 15 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
Female 33 1.37 (0.80, 2.33) 1.36 (0.77, 2.38) 1.20 (0.69, 2.07) 1.23 (0.72, 2.10)
Education (years)          
≥ 12 29 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
< 12 19 1.23 (0.74, 2.05) 1.18 (0.67, 2.08) 0.64 (0.39, 1.07) 0.74 (0.43, 1.26)
BMI (kg/m2)          
< 30 20 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 30 27 1.35 (0.81, 2.25) 1.35 (0.80, 2.28) 1.20 (0.73, 1.98) 1.17 (0.71, 1.95)
Waist circumference (cm)          
< Sex-specific mediana 20 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ Sex-specific median 26 0.90 (0.53, 1.53) 0.88 (0.52, 1.50) 1.05 (0.63, 1.75) 0.99 (0.59, 1.65)
Percent body fat          
< Sex-specific medianb 23 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ Sex-specific median 24 0.94 (0.56, 1.56) 0.90 (0.53, 1.51) 1.47 (0.91, 2.38) 1.58 (0.98, 2.56)
Smoking          
Never 20 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
Ever 28 0.81 (0.49, 1.35) 0.81 (0.47, 1.38) 1.02 (0.61, 1.72) 1.09 (0.65, 1.82)
Alcohol status          
Never 8 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
Ever 40 0.97 (0.49, 1.90) 1.06 (0.46, 2.43) 0.85 (0.43, 1.68) 0.71 (0.32, 1.58)
Urinary arsenic (μg/g)c          
< 7.2 24 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 14.0 24 1.05 (0.64, 1.74) 1.05 (0.61, 1.80) 0.74 (0.44, 1.22) 0.73 (0.44, 1.22)
%iAs          
< 8.5 23 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 8.5 23 0.85 (0.51, 1.43) 0.78 (0.44, 1.39) 0.56 (0.34, 0.92) 0.61 (0.36, 1.01)
%MMA          
< 14.4 23 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 14.4 23 0.73 (0.44, 1.21) 0.78 (0.44, 1.40) 0.59 (0.36, 0.97) 0.71 (0.42, 1.20)
%DMA          
< 78.3 23 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 78.3 23 1.56 (0.95, 2.57) 1.64 (0.93, 2.88) 1.76 (1.07, 2.88) 1.59 (0.95, 2.66)
Cadmium (μg/g)          
< 0.87 24 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 0.87 24 1.64 (1.02, 2.65) 1.75 (0.96, 3.20) 1.16 (0.70, 1.94) 1.08 (0.59, 1.97)
Antimony (μg/g)          
< 0.27 24 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 0.27 24 1.37 (0.84, 2.24) 1.24 (0.71, 2.15) 1.07 (0.64, 1.78) 1.08 (0.64, 1.85)
Tungsten (μg/g)          
< 0.13 24 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 0.13 24 1.50 (0.92, 2.45) 1.46 (0.85, 2.52) 1.25 (0.76, 2.08) 1.13 (0.66, 1.92)
%5-mC          
< 0.32 24 NA NA 1.00 (Ref) 1.00 (Ref)
≥ 0.32 24 NA NA 1.36 (0.82, 2.25) 1.56 (0.95, 2.56)
%5-hmC          
< 0.12 23 1.00 (Ref) 1.00 (Ref) NA NA
≥ 0.12 25 1.63 (1.01, 2.64) 1.93 (1.15, 3.26) NA NA