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 3. Prospective associations [OR (95% CI)] of global DNA methylation (%5-mC) and global DNA hydroxymethylation (%5-hmC) in 1993–1995 (visit 3) by participant characteristics in the Strong Heart Study (SHS).
Characteristic n Methylation Hydroxymethylation
Model 1 Model 2 Model 3 Model 1 Model 2 Model 3
Abbreviations: NA, not available; Ref, referent. Model 1 was unadjusted; model 2 was adjusted for log-transformed total count of white blood cells and percent of neutrophils; and model 3 was adjusted as for model 2 and also 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 21 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 54 23 0.62 (0.34, 1.10) 0.62 (0.35, 1.12) 0.56 (0.31, 1.03) 0.63 (0.38, 1.10) 0.63 (0.38, 1.05) 0.64 (0.37, 1.10)
Sex              
Male 15 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
Female 29 0.76 (0.41, 1.42) 0.80 (0.42, 1.53) 0.69 (0.36, 1.33) 1.20 (0.70, 2.08) 1.24 (0.70, 2.18) 1.16 (0.66, 2.04)
Education (years)              
≥ 12 27 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
< 12 17 1.08 (0.58, 1.99) 1.06 (0.56, 2.01) 1.07 (0.54, 2.09) 1.20 (0.71, 2.05) 1.17 (0.67, 2.04) 1.23 (0.69, 2.19)
BMI (kg/m2)              
< 30 18 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 30 25 1.67 (0.92, 3.05) 1.69 (0.91, 3.14) 1.69 (0.92, 3.10) 1.05 (0.61, 1.80) 1.08 (0.62, 1.89) 1.01 (0.59, 1.73)
Waist circumference (cm)              
< Sex-specific mediana 19 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ Sex-specific median 24 1.19 (0.64, 2.20) 1.16 (0.63, 2.17) 1.16 (0.63, 2.14) 0.86 (0.51, 1.47) 0.85 (0.50, 1.47) 0.82 (0.49, 1.38)
Percent body fat              
< Sex-specific medianb 21 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ Sex-specific median 22 1.61 (0.89, 2.92) 1.60 (0.87, 2.93) 1.45 (0.79, 2.65) 1.48 (0.88, 2.49) 1.50 (0.89, 2.55) 1.41 (0.84, 2.36)
Smoking              
Never 19 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
Ever 25 0.58 (0.32, 1.03) 0.61 (0.33, 1.13) 0.51 (0.27, 0.98) 0.69 (0.41, 1.16) 0.71 (0.41, 1.24) 0.68 (0.39, 1.18)
Alcohol status              
Never 8 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
Ever 36 0.86 (0.40, 1.87) 0.84 (0.38, 1.85) 0.93 (0.35, 2.44) 0.89 (0.45, 1.75) 0.89 (0.45, 1.78) 0.90 (0.39, 2.07)
Urinary arsenic (μg/g)c              
< 7.2 23 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 14.0 21 0.58 (0.33, 1.03) 0.54 (0.30, 0.97) 0.59 (0.32, 1.10) 0.78 (0.46, 1.30) 0.73 (0.43, 1.25) 0.80 (0.46, 1.39)
%iAs              
< 8.5 21 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 8.5 22 0.91 (0.50, 1.68) 0.90 (0.48, 1.67) 0.78 (0.40, 1.50) 0.83 (0.49, 1.40) 0.79 (0.46, 1.37) 0.71 (0.40, 1.25)
%MMA              
< 14.4 21 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 14.4 22 0.73 (0.40, 1.34) 0.73 (0.40, 1.34) 0.70 (0.36, 1.37) 0.58 (0.35, 0.96) 0.58 (0.35, 0.98) 0.62 (0.35, 1.10)
%DMA              
< 78.3 22 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 78.3 21 1.57 (0.87, 2.85) 1.61 (0.88, 2.94) 1.75 (0.92, 3.32) 1.34 (0.79, 2.26) 1.38 (0.81, 2.36) 1.32 (0.75, 2.35)
Cadmium (μg/g)              
< 0.87 24 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 0.87 20 0.86 (0.47, 1.56) 0.90 (0.49, 1.66) 1.03 (0.50, 2.11) 1.04 (0.62, 1.76) 1.07 (0.62, 1.83) 0.97 (0.52, 1.80)
Antimony (μg/g)              
< 0.27 22 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 0.27 22 1.71 (0.96, 3.04) 1.93 (1.07, 3.47) 2.15 (1.15, 4.01) 1.15 (0.69, 1.94) 1.22 (0.71, 2.10) 1.16 (0.65, 2.07)
Tungsten (μg/g)              
< 0.13 23 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 0.13 21 0.84 (0.46, 1.52) 0.90 (0.47, 1.71) 0.93 (0.46, 1.86) 1.25 (0.75, 2.10) 1.40 (0.81, 2.44) 1.32 (0.73, 2.37)
%5-mC              
< 0.32 22 NA NA NA 1.00 (Ref) 1.00 (Ref) 1.00 (Ref)
≥ 0.32 22 NA NA NA 1.24 (0.74, 2.08) 1.21 (0.71, 2.06) 1.15 (0.67, 1.96)
%5-hmC              
< 0.12 20 1.00 (Ref) 1.00 (Ref) 1.00 (Ref) NA NA NA
≥ 0.12 24 1.23 (0.68, 2.24) 1.16 (0.63, 2.16) 1.28 (0.67, 2.45) NA NA NA