Introduction
Methods
Study population
Characteristics | All (N = 364) | Groups | p-valuea | |
---|---|---|---|---|
Controls (N = 184) | CHD cases (N = 180) | |||
Age (median, IQR) | 64(58–70) | 63(57–68) | 66(58–73) | 0.008 |
Male (%) | 223(61.3%) | 114(62.0%) | 109(60.6%) | 0.784 |
Hypertension (%) | 214(58.8%) | 84(45.7%) | 130(72.2%) | 2.00E−06 |
Diabetes (%) | 107(29.4%) | 45(24.5%) | 62(34.4%) | 0.063 |
Smoking (%) | 126(34.6%) | 53(28.8%) | 73(40.6%) | 0.027 |
Drinking (%) | 118(32.4%) | 66(35.9%) | 52(28.9%) | 0.116 |
TC, mmol/L | 4.01(3.38–4.8) | 4.26(3.61–5.06) | 3.81(3.25–4.42) | 0.001 |
TG, mmol/L | 1.35(1.00–1.95) | 1.39(1.06–2.17) | 1.30(0.95–1.86) | 0.147 |
HDL, mmol/L | 1.12(0.91–1.34) | 1.15(0.91–1.36) | 1.09(0.91–1.31) | 0.290 |
LDL, mmol/L | 2.51(1.94–3.19) | 2.69(2.06–3.40) | 2.28(1.82–2.87) | 2.00E−04 |
Sample collection and processing
Matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry
Statistical analyses
Results
Association between blood-based 6p21.33 and AHRR methylation and CHD
CpG sites | Controls (N = 184) | CHD cases (N = 180) | OR (95%CI) per-10%methylation | p-valuea | p-value* | OR (95%CI) per-10%methylation | p-valueb | p-value# |
---|---|---|---|---|---|---|---|---|
Median (IQR) | Median (IQR) | |||||||
6p21.33_CpG_1 | 1.00(0.99–1.00) | 1.00(0.98–1.00) | 0.96(0.59–1.54) | 0.852 | 1.000 | 1.01(0.60–1.68) | 0.976 | 1.000 |
6p21.33_CpG_2 | 0.93(0.90–0.95) | 0.94(0.91–0.97) | 0.59(0.36–0.94) | 0.027 | 0.108 | 0.64(0.39–1.06) | 0.083 | 0.332 |
6p21.33_CpG_3 | 0.63(0.57–0.70) | 0.62(0.54–0.70) | 1.11(0.94–1.31) | 0.235 | 1.000 | 1.14(0.95–1.37) | 0.152 | 0.608 |
6p21.33_CpG_4.5/cg06126421 | 0.50(0.45–0.55) | 0.48(0.42–0.52) | 1.42(1.10–1.83) | 0.008 | 0.032 | 1.40(1.07–1.83) | 0.016 | 0.064 |
AHRR_CpG_1 | 0.73(0.63–0.80) | 0.74(0.58–0.83) | 1.01(0.90–1.14) | 0.846 | 1.000 | 1.00(0.87–1.14) | 0.959 | 1.000 |
AHRR_CpG_2 | 0.87(0.74–0.96) | 0.89(0.72–1.00) | 1.02(0.90–1.16) | 0.720 | 1.000 | 1.15(0.82–1.60) | 0.419 | 1.000 |
AHRR_CpG_3/cg05575921 | 0.77(0.64–0.83) | 0.75(0.59–0.85) | 1.08(0.96–1.22) | 0.201 | 1.000 | 1.02(0.86–1.20) | 0.866 | 1.000 |
AHRR_CpG_4.5 | 0.77(0.68–0.84) | 0.75(0.60–0.84) | 1.12(0.99–1.27) | 0.075 | 0.750 | 1.07(0.77–1.49) | 0.696 | 1.000 |
AHRR_CpG_6 | 0.84(0.74–0.90) | 0.82(0.65–0.91) | 1.10(0.96–1.26) | 0.177 | 1.000 | 1.03(0.89–1.18) | 0.691 | 1.000 |
AHRR_CpG_7 | 0.66(0.53–0.76) | 0.66(0.53–0.79) | 1.01(0.89–1.16) | 0.836 | 1.000 | 1.07(0.94–1.22) | 0.341 | 1.000 |
AHRR_CpG_8.9 | 0.85(0.73–0.94) | 0.87(0.76–0.94) | 0.89(0.73–1.09) | 0.270 | 1.000 | 1.15(1.00–1.32) | 0.052 | 0.520 |
AHRR_CpG_10.11 | 0.92(0.89–0.95) | 0.92(0.87–0.96) | 1.25(0.91–1.71) | 0.170 | 1.000 | 1.08(0.93–1.26) | 0.315 | 1.000 |
AHRR_CpG_12 | 0.88(0.81–0.95) | 0.88(0.78–0.98) | 1.07(0.91–1.25) | 0.420 | 1.000 | 0.99(0.85–1.14) | 0.846 | 1.000 |
AHRR_CpG_14.15 | 0.94(0.91–0.95) | 0.94(0.90–0.97) | 1.08(0.80–1.47) | 0.618 | 1.000 | 0.89(0.72–1.09) | 0.260 | 1.000 |
Methylation difference of 6p21.33 and AHRR between patients with heart failure, MI, non-MI CHD, and controls
CpG sites | Controls (N = 184) | Heart failure cases (N = 145) | OR (95%CI) per-10%methylation | p-valuea | p-value* | OR (95%CI) per-10%methylation | p-valueb | p-value# |
---|---|---|---|---|---|---|---|---|
Median (IQR) | Median (IQR) | |||||||
Panel (A). Heart failure cases vs. Controls | ||||||||
6p21.33_CpG_1 | 1.00(0.99–1.00) | 1.00(0.99–1.00) | 0.75(0.44–1.30) | 0.308 | 1.000 | 0.78(0.44–1.38) | 0.398 | 1.000 |
6p21.33_CpG_2 | 0.93(0.90–0.95) | 0.94(0.91–0.96) | 0.52(0.30–0.89) | 0.017 | 0.068 | 0.56(0.31–0.98) | 0.044 | 0.176 |
6p21.33_CpG_3 | 0.63(0.57–0.70) | 0.61(0.53–0.69) | 1.16(0.97–1.40) | 0.113 | 0.452 | 1.19(0.98–1.45) | 0.079 | 0.316 |
6p21.33_CpG_4.5/cg06126421 | 0.50(0.45–0.55) | 0.48(0.42–0.52) | 1.62(1.21–2.17) | 0.001 | 0.004 | 1.59(1.17–2.16) | 0.003 | 0.012 |
AHRR_CpG_1 | 0.73(0.63–0.80) | 0.74(0.56–0.82) | 1.04(0.91–1.18) | 0.607 | 1.000 | 1.02(0.89–1.18) | 0.775 | 1.000 |
AHRR_CpG_2 | 0.87(0.74–0.96) | 0.88(0.70–1.00) | 1.08(0.94–1.24) | 0.267 | 1.000 | 1.10(0.94–1.28) | 0.246 | 1.000 |
AHRR_CpG_3/cg05575921 | 0.77(0.64–0.83) | 0.75(0.59–0.84) | 1.09(0.96–1.24) | 0.200 | 1.000 | 1.08(0.93–1.24) | 0.319 | 1.000 |
AHRR_CpG_4.5 | 0.77(0.68–0.84) | 0.74(0.59–0.84) | 1.16(1.01–1.34) | 0.031 | 0.310 | 1.19(1.02–1.38) | 0.024 | 0.240 |
AHRR_CpG_6 | 0.84(0.74–0.90) | 0.82(0.65–0.91) | 1.12(0.96–1.30) | 0.140 | 1.000 | 1.11(0.94–1.32) | 0.217 | 1.000 |
AHRR_CpG_7 | 0.66(0.53–0.76) | 0.67(0.54–0.82) | 1.05(0.91–1.21) | 0.529 | 1.000 | 1.02(0.87–1.18) | 0.850 | 1.000 |
AHRR_CpG_8.9 | 0.85(0.73–0.94) | 0.89(0.77–0.95) | 0.95(0.77–1.18) | 0.664 | 1.000 | 0.93(0.74–1.17) | 0.542 | 1.000 |
AHRR_CpG_10.11 | 0.92(0.89–0.95) | 0.92(0.88–0.95) | 1.07(0.70–1.63) | 0.762 | 1.000 | 0.96(0.61–1.51) | 0.855 | 1.000 |
AHRR_CpG_12 | 0.88(0.81–0.95) | 0.88(0.79–0.97) | 1.03(0.85–1.24) | 0.793 | 1.000 | 0.97(0.80–1.19) | 0.798 | 1.000 |
AHRR_CpG_14.15 | 0.94(0.91–0.95) | 0.94(0.90–0.97) | 1.03(0.75–1.43) | 0.841 | 1.000 | 1.04(0.74–1.45) | 0.828 | 1.000 |
CpG sites | Controls (N = 184) | MI cases (N = 78) | OR (95%CI) per-10%methylation | p-valuea | p-value* | OR (95%CI) per-10%methylation | p-valueb | p-value# |
---|---|---|---|---|---|---|---|---|
Median (IQR) | Median (IQR) | |||||||
Panel (B). MI cases vs. Controls | ||||||||
6p21.33_CpG_1 | 1.00(0.99–1.00) | 1.00(0.97–1.00) | 1.60(0.87–2.92) | 0.128 | 0.512 | 1.54(0.83–2.87) | 0.173 | 0.692 |
6p21.33_CpG_2 | 0.93(0.90–0.95) | 0.94(0.89–0.97) | 0.64(0.35–1.18) | 0.156 | 0.624 | 0.64(0.34–1.21) | 0.170 | 0.680 |
6p21.33_CpG_3 | 0.63(0.57–0.70) | 0.62(0.53–0.70) | 1.17(0.95–1.44) | 0.150 | 0.600 | 1.17(0.94–1.45) | 0.161 | 0.644 |
6p21.33_CpG_4.5/cg06126421 | 0.50(0.45–0.55) | 0.48(0.40–0.51) | 1.45(1.04–2.02) | 0.030 | 0.120 | 1.42(1.01–1.99) | 0.042 | 0.168 |
AHRR_CpG_1 | 0.73(0.63–0.80) | 0.68(0.53–0.82) | 1.07(0.92–1.24) | 0.411 | 1.000 | 1.05(0.89–1.23) | 0.584 | 1.000 |
AHRR_CpG_2 | 0.87(0.74–0.96) | 0.84(0.62–0.98) | 1.07(0.92–1.25) | 0.394 | 1.000 | 1.06(0.90–1.25) | 0.505 | 1.000 |
AHRR_CpG_3/cg05575921 | 0.77(0.64–0.83) | 0.72(0.50–0.84) | 1.10(0.96–1.27) | 0.179 | 1.000 | 1.08(0.92–1.25) | 0.344 | 1.000 |
AHRR_CpG_4.5 | 0.77(0.68–0.84) | 0.74(0.54–0.83) | 1.15(0.99–1.35) | 0.073 | 0.730 | 1.15(0.98–1.36) | 0.093 | 0.930 |
AHRR_CpG_6 | 0.84(0.74–0.90) | 0.79(0.61–0.91) | 1.15(0.97–1.35) | 0.100 | 1.000 | 1.12(0.94–1.33) | 0.207 | 1.000 |
AHRR_CpG_7 | 0.66(0.53–0.76) | 0.61(0.49–0.73) | 1.06(0.89–1.26) | 0.526 | 1.000 | 1.03(0.86–1.23) | 0.778 | 1.000 |
AHRR_CpG_8.9 | 0.85(0.73–0.94) | 0.82(0.69–0.92) | 0.99(0.77–1.29) | 0.966 | 1.000 | 0.97(0.75–1.27) | 0.838 | 1.000 |
AHRR_CpG_10.11 | 0.92(0.89–0.95) | 0.92(0.85–0.96) | 1.47(1.01–2.14) | 0.042 | 0.420 | 1.39(0.95–2.04) | 0.091 | 0.910 |
AHRR_CpG_12 | 0.88(0.81–0.95) | 0.87(0.75–1.00) | 1.12(0.92–1.37) | 0.245 | 1.000 | 1.08(0.88–1.32) | 0.450 | 1.000 |
AHRR_CpG_14.15 | 0.94(0.91–0.95) | 0.94(0.87–0.97) | 1.38(0.84–2.27) | 0.210 | 1.000 | 1.41(0.83–2.38) | 0.203 | 1.000 |
CpG sites | Controls (N = 184) | Non-MI CHD cases (N = 102) | OR (95%CI) per-10%methylation | p-valuea | p-value* | OR (95%CI) per-10%methylation | p-valueb | p-value# |
---|---|---|---|---|---|---|---|---|
Median (IQR) | Median (IQR) | |||||||
Panel (C). Non-MI CHD cases vs. Controls | ||||||||
6p21.33_CpG_1 | 1.00(0.99–1.00) | 1.00(0.99–1.00) | 0.54(0.28–1.04) | 0.064 | 0.256 | 0.56(0.29–1.11) | 0.095 | 0.380 |
6p21.33_CpG_2 | 0.93(0.90–0.95) | 0.94(0.92–0.97) | 0.55(0.29–1.03) | 0.061 | 0.244 | 0.70(0.35–1.39) | 0.302 | 1.000 |
6p21.33_CpG_3 | 0.63(0.57–0.70) | 0.62(0.55–0.70) | 1.09(0.87–1.37) | 0.448 | 1.000 | 1.16(0.91–1.48) | 0.220 | 0.880 |
6p21.33_CpG_4.5/cg06126421 | 0.50(0.45–0.55) | 0.48(0.44–0.52) | 1.41(1.01–1.98) | 0.047 | 0.188 | 1.39(0.97–1.99) | 0.077 | 0.308 |
AHRR_CpG_1 | 0.73(0.63–0.80) | 0.77(0.60–0.83) | 0.96(0.81–1.12) | 0.581 | 1.000 | 0.92(0.77–1.11) | 0.400 | 1.000 |
AHRR_CpG_2 | 0.87(0.74–0.96) | 0.91(0.76–1.00) | 0.99(0.82–1.18) | 0.863 | 1.000 | 0.99(0.81–1.22) | 0.948 | 1.000 |
AHRR_CpG_3/cg05575921 | 0.77(0.64–0.83) | 0.77(0.62–0.85) | 1.06(0.90–1.25) | 0.456 | 1.000 | 1.09(0.90–1.31) | 0.373 | 1.000 |
AHRR_CpG_4.5 | 0.77(0.68–0.84) | 0.76(0.62–0.85) | 1.14(0.96–1.34) | 0.128 | 1.000 | 1.20(0.99–1.45) | 0.059 | 0.590 |
AHRR_CpG_6 | 0.84(0.74–0.90) | 0.84(0.71–0.91) | 1.05(0.87–1.26) | 0.641 | 1.000 | 1.03(0.83–1.29) | 0.774 | 1.000 |
AHRR_CpG_7 | 0.66(0.53–0.76) | 0.70(0.57–0.83) | 0.97(0.82–1.15) | 0.753 | 1.000 | 0.95(0.78–1.14) | 0.567 | 1.000 |
AHRR_CpG_8.9 | 0.85(0.73–0.94) | 0.89(0.79–0.96) | 0.81(0.62–1.05) | 0.115 | 1.000 | 0.80(0.60–1.06) | 0.112 | 1.000 |
AHRR_CpG_10.11 | 0.92(0.89–0.95) | 0.92(0.88–0.96) | 1.10(0.69–1.76) | 0.680 | 1.000 | 1.00(0.61–1.65) | 0.988 | 1.000 |
AHRR_CpG_12 | 0.88(0.81–0.95) | 0.89(0.80–0.96) | 1.07(0.86–1.34) | 0.550 | 1.000 | 1.04(0.81–1.33) | 0.770 | 1.000 |
AHRR_CpG_14.15 | 0.94(0.91–0.95) | 0.94(0.92–0.97) | 1.01(0.70–1.44) | 0.968 | 1.000 | 1.00(0.69–1.43) | 0.984 | 1.000 |
Association between blood-based 6p21.33 and AHRR methylation and early CHD cases
CpG sites | Controls (N = 184) | NYHA I&II CHD cases (N = 124) | OR (95%CI) per-10%methylation | p-valuea | p-value* | OR (95%CI) per-10%methylation | p-valueb | p-value# |
---|---|---|---|---|---|---|---|---|
Median (IQR) | Median (IQR) | |||||||
6p21.33_CpG_1 | 1.00(0.99–1.00) | 1.00(1.00–1.00) | 0.79(0.49–1.27) | 0.328 | 1.000 | 0.78(0.48–1.27) | 0.315 | 1.000 |
6p21.33_CpG_2 | 0.93(0.90–0.95) | 0.94(0.91–0.97) | 0.49(0.28–0.85) | 0.011 | 0.044 | 0.54(0.30–0.97) | 0.038 | 0.152 |
6p21.33_CpG_3 | 0.63(0.57–0.70) | 0.62(0.53–0.69) | 1.15(0.94–1.41) | 0.164 | 0.656 | 1.21(0.98–1.50) | 0.079 | 0.316 |
6p21.33_CpG_4.5/cg06126421 | 0.50(0.45–0.55) | 0.49(0.44–0.52) | 1.69(1.22–2.34) | 0.002 | 0.008 | 1.65(1.17–2.34) | 0.005 | 0.020 |
AHRR_CpG_1 | 0.73(0.63–0.80) | 0.74(0.59–0.82) | 1.04(0.90–1.20) | 0.592 | 1.000 | 1.03(0.88–1.21) | 0.736 | 1.000 |
AHRR_CpG_2 | 0.87(0.74–0.96) | 0.89(0.72–1.00) | 1.04(0.89–1.21) | 0.618 | 1.000 | 1.06(0.89–1.26) | 0.508 | 1.000 |
AHRR_CpG_3/cg05575921 | 0.77(0.64–0.83) | 0.75(0.60–0.85) | 1.10(0.95–1.26) | 0.201 | 1.000 | 1.11(0.94–1.30) | 0.211 | 1.000 |
AHRR_CpG_4.5 | 0.77(0.68–0.84) | 0.76(0.61–0.84) | 1.13(0.97–1.31) | 0.115 | 1.000 | 1.16(0.98–1.37) | 0.081 | 0.810 |
AHRR_CpG_6 | 0.84(0.74–0.90) | 0.83(0.68–0.90) | 1.11(0.94–1.31) | 0.239 | 1.000 | 1.10(0.91–1.33) | 0.316 | 1.000 |
AHRR_CpG_7 | 0.66(0.53–0.76) | 0.69(0.55–0.82) | 1.02(0.88–1.19) | 0.772 | 1.000 | 1.01(0.85–1.19) | 0.930 | 1.000 |
AHRR_CpG_8.9 | 0.85(0.73–0.94) | 0.89(0.78–0.94) | 0.92(0.74–1.16) | 0.488 | 1.000 | 0.91(0.72–1.15) | 0.436 | 1.000 |
AHRR_CpG_10.11 | 0.92(0.89–0.95) | 0.92(0.88–0.95) | 1.02(0.65–1.60) | 0.929 | 1.000 | 0.93(0.57–1.51) | 0.756 | 1.000 |
AHRR_CpG_12 | 0.88(0.81–0.95) | 0.89(0.80–0.95) | 1.05(0.86–1.29) | 0.620 | 1.000 | 1.03(0.83–1.28) | 0.792 | 1.000 |
AHRR_CpG_14.15 | 0.94(0.91–0.95) | 0.94(0.91–0.96) | 1.08(0.77–1.50) | 0.670 | 1.000 | 1.09(0.76–1.57) | 0.649 | 1.000 |
The correlation between blood-based 6p21.33 and AHRR methylation and CHD-related characteristics
Characteristics | Group (N) | Median of methylation intensity | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
6p21.33_CpG_1 | 6p21.33_CpG_2 | 6p21.33_CpG_3 | 6p21.33_CpG_4.5/cg06126421 | AHRR_CpG_1 | AHRR_CpG_2 | AHRR_CpG_3/cg05575921 | AHRR_CpG_4.5 | AHRR_CpG_6 | AHRR_CpG_7 | AHRR_CpG_8.9 | AHRR_CpG_10.11 | AHRR_CpG_12 | AHRR_CpG_14.15 | ||
CHD cases | |||||||||||||||
Age (180) | < 65 (83) | 1.00 | 0.94 | 0.64 | 0.48 | 0.77 | 0.90 | 0.75 | 0.74 | 0.82 | 0.66 | 0.87 | 0.92 | 0.88 | 0.94 |
≥ 65 (97) | 1.00 | 0.94 | 0.61 | 0.48 | 0.69 | 0.89 | 0.76 | 0.76 | 0.82 | 0.66 | 0.87 | 0.92 | 0.89 | 0.94 | |
p-valuea | 0.894 | 0.998 | 0.143 | 1.000 | 0.050 | 0.617 | 0.875 | 0.812 | 0.661 | 0.583 | 0.624 | 0.166 | 0.884 | 0.870 | |
Gender (180) | Female (71) | 1.00 | 0.94 | 0.65 | 0.49 | 0.78 | 0.97 | 0.81 | 0.79 | 0.88 | 0.71 | 0.88 | 0.93 | 0.91 | 0.94 |
Male (109) | 1.00 | 0.93 | 0.60 | 0.47 | 0.66 | 0.83 | 0.70 | 0.73 | 0.76 | 0.63 | 0.86 | 0.91 | 0.86 | 0.94 | |
p-valuea | 0.646 | 0.136 | 0.009 | 0.050 | 0.003 | 1.00E−06 | 1.00E−05 | 0.003 | 7.60E−05 | 0.039 | 0.206 | 0.148 | 0.039 | 0.144 | |
Smoking (180) | No (107) | 1.00 | 0.94 | 0.63 | 0.49 | 0.78 | 0.94 | 0.80 | 0.78 | 0.86 | 0.70 | 0.86 | 0.93 | 0.90 | 0.94 |
Yes (73) | 1.00 | 0.94 | 0.59 | 0.45 | 0.63 | 0.76 | 0.62 | 0.65 | 0.71 | 0.61 | 0.87 | 0.90 | 0.84 | 0.94 | |
p-valuea | 0.372 | 0.615 | 0.017 | 0.005 | 0.001 | 2.00E−06 | 2.15E−07 | 0.001 | 3.20E−05 | 0.011 | 0.381 | 0.001 | 0.028 | 0.483 | |
Drinking (180) | No (128) | 1.00 | 0.93 | 0.62 | 0.49 | 0.75 | 0.91 | 0.77 | 0.76 | 0.83 | 0.66 | 0.86 | 0.92 | 0.89 | 0.94 |
Yes (52) | 1.00 | 0.95 | 0.62 | 0.48 | 0.64 | 0.84 | 0.64 | 0.73 | 0.76 | 0.66 | 0.89 | 0.91 | 0.86 | 0.94 | |
p-valuea | 0.075 | 0.189 | 0.560 | 0.332 | 0.127 | 0.063 | 0.011 | 0.321 | 0.101 | 0.706 | 0.580 | 0.227 | 0.465 | 0.575 | |
Hypertension (180) | Not prevalent (50) | 1.00 | 0.93 | 0.62 | 0.47 | 0.70 | 0.84 | 0.73 | 0.73 | 0.78 | 0.61 | 0.85 | 0.92 | 0.91 | 0.95 |
Prevalent (130) | 1.00 | 0.94 | 0.62 | 0.49 | 0.74 | 0.89 | 0.76 | 0.76 | 0.83 | 0.66 | 0.87 | 0.92 | 0.88 | 0.94 | |
p-valuea | 0.345 | 0.117 | 0.166 | 0.318 | 0.375 | 0.170 | 0.592 | 0.102 | 0.154 | 0.332 | 0.280 | 0.742 | 0.428 | 0.459 | |
Diabetes (180) | Not prevalent (118) | 1.00 | 0.93 | 0.61 | 0.49 | 0.74 | 0.88 | 0.74 | 0.74 | 0.80 | 0.64 | 0.85 | 0.92 | 0.86 | 0.94 |
Prevalent (62) | 1.00 | 0.95 | 0.63 | 0.47 | 0.73 | 0.92 | 0.77 | 0.76 | 0.84 | 0.72 | 0.89 | 0.92 | 0.89 | 0.95 | |
p-valuea | 0.589 | 0.064 | 0.300 | 0.699 | 0.908 | 0.119 | 0.191 | 0.343 | 0.341 | 0.021 | 0.095 | 0.392 | 0.376 | 0.422 | |
TC (180) | < 5.0 mmol/L (153) | 1.00 | 0.94 | 0.62 | 0.48 | 0.72 | 0.89 | 0.74 | 0.74 | 0.81 | 0.64 | 0.87 | 0.92 | 0.88 | 0.94 |
≥ 5.0 mmol/L (27) | 1.00 | 0.93 | 0.64 | 0.48 | 0.77 | 0.93 | 0.77 | 0.76 | 0.89 | 0.72 | 0.86 | 0.92 | 0.90 | 0.94 | |
p-valuea | 0.998 | 0.748 | 0.732 | 0.905 | 0.286 | 0.355 | 0.198 | 0.739 | 0.085 | 0.283 | 0.823 | 0.542 | 0.166 | 0.594 | |
TG (180) | < 1.70 mmol/L (123) | 1.00 | 0.94 | 0.62 | 0.48 | 0.74 | 0.89 | 0.77 | 0.74 | 0.82 | 0.66 | 0.87 | 0.92 | 0.88 | 0.94 |
≥ 1.70 mmol/L (57) | 1.00 | 0.93 | 0.62 | 0.48 | 0.72 | 0.89 | 0.73 | 0.76 | 0.83 | 0.66 | 0.86 | 0.92 | 0.89 | 0.95 | |
p-valuea | 0.558 | 0.999 | 0.843 | 0.775 | 0.841 | 0.904 | 0.356 | 0.304 | 0.463 | 0.763 | 0.255 | 0.762 | 0.900 | 0.268 | |
HDL (180) | < 1.0 mmol/L (67) | 1.00 | 0.94 | 0.60 | 0.46 | 0.72 | 0.87 | 0.73 | 0.73 | 0.77 | 0.64 | 0.86 | 0.92 | 0.87 | 0.94 |
≥ 1.0 mmol/L (113) | 1.00 | 0.94 | 0.63 | 0.49 | 0.74 | 0.90 | 0.76 | 0.76 | 0.84 | 0.67 | 0.87 | 0.92 | 0.89 | 0.94 | |
p-valuea | 0.466 | 0.691 | 0.124 | 0.236 | 0.951 | 0.194 | 0.347 | 0.099 | 0.034 | 0.522 | 0.523 | 0.295 | 0.086 | 0.686 | |
LDL (180) | < 3.0 mmol/L (143) | 1.00 | 0.94 | 0.61 | 0.48 | 0.73 | 0.89 | 0.75 | 0.74 | 0.81 | 0.64 | 0.87 | 0.92 | 0.88 | 0.94 |
≥ 3.0 mmol/L (37) | 1.00 | 0.93 | 0.65 | 0.49 | 0.76 | 0.89 | 0.77 | 0.76 | 0.89 | 0.68 | 0.86 | 0.92 | 0.89 | 0.94 | |
p-valuea | 0.417 | 0.924 | 0.145 | 0.296 | 0.366 | 0.336 | 0.991 | 0.208 | 0.083 | 0.383 | 0.935 | 0.745 | 0.098 | 0.456 | |
Controls | |||||||||||||||
Age (184) | < 65 (119) | 1.00 | 0.93 | 0.64 | 0.50 | 0.73 | 0.87 | 0.76 | 0.77 | 0.82 | 0.69 | 0.87 | 0.92 | 0.88 | 0.93 |
≥ 65 (65) | 1.00 | 0.93 | 0.62 | 0.50 | 0.74 | 0.86 | 0.77 | 0.76 | 0.84 | 0.61 | 0.79 | 0.93 | 0.89 | 0.94 | |
p-valuea | 0.326 | 0.931 | 0.297 | 0.572 | 0.954 | 0.546 | 0.964 | 0.598 | 0.978 | 0.027 | 0.016 | 0.973 | 0.916 | 0.105 | |
Gender (184) | Female (70) | 1.00 | 0.93 | 0.67 | 0.53 | 0.77 | 0.92 | 0.79 | 0.80 | 0.85 | 0.66 | 0.80 | 0.93 | 0.92 | 0.94 |
Male (114) | 1.00 | 0.92 | 0.62 | 0.49 | 0.70 | 0.83 | 0.74 | 0.74 | 0.81 | 0.66 | 0.87 | 0.92 | 0.87 | 0.93 | |
p-valuea | 0.052 | 0.130 | 0.004 | 4.17E−04 | 0.001 | 2.00E−06 | 0.008 | 0.002 | 0.048 | 0.815 | 0.128 | 0.284 | 0.004 | 0.672 | |
Smoking (180) | No (127) | 1.00 | 0.93 | 0.64 | 0.51 | 0.76 | 0.89 | 0.79 | 0.78 | 0.85 | 0.68 | 0.85 | 0.93 | 0.90 | 0.94 |
Yes (53) | 1.00 | 0.92 | 0.62 | 0.48 | 0.62 | 0.75 | 0.67 | 0.69 | 0.76 | 0.59 | 0.85 | 0.91 | 0.85 | 0.93 | |
p-valuea | 0.526 | 0.916 | 0.684 | 0.065 | 2.00E−06 | 1.00E-06 | 1.22E-04 | 0.001 | 0.001 | 0.063 | 0.911 | 0.019 | 0.010 | 0.132 | |
Drinking (180) | No (114) | 1.00 | 0.93 | 0.63 | 0.50 | 0.76 | 0.88 | 0.78 | 0.78 | 0.84 | 0.63 | 0.80 | 0.92 | 0.89 | 0.94 |
Yes (66) | 1.00 | 0.93 | 0.64 | 0.51 | 0.69 | 0.85 | 0.73 | 0.75 | 0.82 | 0.71 | 0.90 | 0.93 | 0.88 | 0.94 | |
p-valuea | 0.508 | 0.982 | 0.450 | 0.422 | 0.010 | 0.084 | 0.060 | 0.318 | 0.308 | 0.030 | 0.002 | 0.391 | 0.283 | 0.687 | |
Hypertension (177) | Not prevalent (93) | 1.00 | 0.92 | 0.62 | 0.50 | 0.75 | 0.87 | 0.77 | 0.76 | 0.85 | 0.68 | 0.86 | 0.92 | 0.88 | 0.93 |
Prevalent (84) | 1.00 | 0.93 | 0.65 | 0.50 | 0.72 | 0.85 | 0.75 | 0.77 | 0.82 | 0.63 | 0.82 | 0.92 | 0.88 | 0.94 | |
p-valuea | 0.879 | 0.343 | 0.608 | 0.745 | 0.819 | 0.972 | 0.732 | 0.776 | 0.336 | 0.465 | 0.810 | 0.735 | 0.806 | 0.336 | |
Diabetes (177) | Not prevalent (132) | 1.00 | 0.92 | 0.64 | 0.50 | 0.74 | 0.87 | 0.78 | 0.77 | 0.84 | 0.65 | 0.82 | 0.92 | 0.89 | 0.93 |
Prevalent (45) | 1.00 | 0.93 | 0.62 | 0.51 | 0.72 | 0.85 | 0.73 | 0.75 | 0.82 | 0.69 | 0.88 | 0.92 | 0.87 | 0.94 | |
p-valuea | 0.796 | 0.043 | 0.719 | 0.769 | 0.802 | 0.356 | 0.217 | 0.616 | 0.514 | 0.721 | 0.402 | 0.653 | 0.434 | 0.528 | |
TC (180) | < 5.0 mmol/L (131) | 1.00 | 0.93 | 0.64 | 0.50 | 0.74 | 0.86 | 0.76 | 0.76 | 0.83 | 0.65 | 0.84 | 0.93 | 0.89 | 0.94 |
≥ 5.0 mmol/L (49) | 1.00 | 0.93 | 0.62 | 0.51 | 0.70 | 0.87 | 0.75 | 0.78 | 0.84 | 0.69 | 0.88 | 0.92 | 0.87 | 0.92 | |
p-valuea | 0.992 | 0.464 | 0.959 | 0.506 | 0.698 | 0.516 | 0.524 | 0.559 | 0.930 | 0.798 | 0.079 | 0.586 | 0.107 | 0.001 | |
TG (178) | < 1.70 mmol/L (114) | 1.00 | 0.93 | 0.62 | 0.50 | 0.75 | 0.87 | 0.78 | 0.78 | 0.84 | 0.65 | 0.83 | 0.93 | 0.90 | 0.94 |
≥ 1.70 mmol/L (64) | 1.00 | 0.93 | 0.65 | 0.50 | 0.70 | 0.85 | 0.73 | 0.75 | 0.83 | 0.70 | 0.88 | 0.92 | 0.87 | 0.93 | |
p-valuea | 0.018 | 0.755 | 0.891 | 0.759 | 0.482 | 0.434 | 0.037 | 0.128 | 0.647 | 0.174 | 0.137 | 0.781 | 0.157 | 0.332 | |
HDL (180) | < 1.0 mmol/L (63) | 1.00 | 0.93 | 0.62 | 0.50 | 0.70 | 0.85 | 0.73 | 0.75 | 0.81 | 0.69 | 0.87 | 0.92 | 0.87 | 0.94 |
≥ 1.0 mmol/L (117) | 1.00 | 0.93 | 0.64 | 0.51 | 0.75 | 0.88 | 0.77 | 0.78 | 0.85 | 0.65 | 0.85 | 0.93 | 0.90 | 0.93 | |
p-valuea | 0.440 | 0.735 | 0.260 | 0.375 | 0.429 | 0.170 | 0.120 | 0.135 | 0.185 | 0.420 | 0.279 | 0.866 | 0.334 | 0.112 | |
LDL (180) | < 3.0 mmol/L (108) | 1.00 | 0.93 | 0.64 | 0.51 | 0.73 | 0.85 | 0.75 | 0.76 | 0.84 | 0.65 | 0.85 | 0.93 | 0.88 | 0.94 |
≥ 3.0 mmol/L (72) | 1.00 | 0.93 | 0.62 | 0.50 | 0.75 | 0.87 | 0.79 | 0.78 | 0.82 | 0.67 | 0.87 | 0.92 | 0.89 | 0.93 | |
p-valuea | 0.822 | 0.720 | 0.651 | 0.572 | 0.655 | 0.345 | 0.659 | 0.626 | 0.731 | 0.966 | 0.231 | 0.635 | 0.957 | 0.021 |
Medicine | Group (N) | Median of methylation intensity | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
6p21.33_CpG_1 | 6p21.33_CpG_2 | 6p21.33_CpG_3 | 6p21.33_CpG_4.5/cg06126421 | AHRR_CpG_1 | AHRR_CpG_2 | AHRR_CpG_3/cg05575921 | AHRR_CpG_4.5 | AHRR_CpG_6 | AHRR_CpG_7 | AHRR_CpG_8.9 | AHRR_CpG_10.11 | AHRR_CpG_12 | AHRR_CpG_14.15 | ||
ACEI | No (147) | 1.00 | 0.94 | 0.62 | 0.49 | 0.73 | 0.90 | 0.75 | 0.76 | 0.83 | 0.67 | 0.87 | 0.92 | 0.87 | 0.94 |
Yes (33) | 1.00 | 0.95 | 0.61 | 0.45 | 0.78 | 0.77 | 0.77 | 0.66 | 0.77 | 0.63 | 0.84 | 0.92 | 0.91 | 0.94 | |
p-value* | 0.334 | 0.411 | 0.660 | 0.134 | 0.723 | 0.035 | 0.988 | 0.092 | 0.278 | 0.050 | 0.343 | 0.474 | 0.297 | 0.543 | |
ARB | No (139) | 1.00 | 0.93 | 0.62 | 0.48 | 0.74 | 0.88 | 0.76 | 0.75 | 0.82 | 0.64 | 0.87 | 0.92 | 0.89 | 0.94 |
Yes (41) | 1.00 | 0.95 | 0.64 | 0.50 | 0.71 | 0.90 | 0.73 | 0.75 | 0.79 | 0.71 | 0.86 | 0.92 | 0.85 | 0.93 | |
p-value* | 0.417 | 0.319 | 0.278 | 0.111 | 0.412 | 0.880 | 0.349 | 0.892 | 0.539 | 0.154 | 0.996 | 0.369 | 0.171 | 0.342 | |
CCB | No (126) | 1.00 | 0.94 | 0.63 | 0.48 | 0.74 | 0.89 | 0.77 | 0.75 | 0.83 | 0.67 | 0.87 | 0.91 | 0.88 | 0.94 |
Yes (54) | 1.00 | 0.94 | 0.60 | 0.49 | 0.69 | 0.89 | 0.74 | 0.76 | 0.81 | 0.64 | 0.85 | 0.92 | 0.88 | 0.94 | |
p-value* | 0.701 | 0.414 | 0.040 | 0.812 | 0.557 | 0.641 | 0.106 | 0.980 | 0.710 | 0.816 | 0.666 | 0.359 | 0.844 | 0.994 | |
β blocker | No (64) | 1.00 | 0.94 | 0.61 | 0.48 | 0.71 | 0.92 | 0.77 | 0.76 | 0.81 | 0.67 | 0.88 | 0.92 | 0.88 | 0.94 |
Yes (116) | 1.00 | 0.94 | 0.63 | 0.48 | 0.74 | 0.88 | 0.75 | 0.74 | 0.82 | 0.64 | 0.86 | 0.92 | 0.88 | 0.94 | |
p-value* | 0.352 | 0.328 | 0.651 | 0.845 | 0.492 | 0.294 | 0.622 | 0.684 | 0.813 | 0.263 | 0.612 | 0.948 | 0.664 | 0.271 | |
Spironolactone | No (143) | 1.00 | 0.93 | 0.62 | 0.48 | 0.74 | 0.89 | 0.75 | 0.75 | 0.82 | 0.67 | 0.87 | 0.92 | 0.87 | 0.94 |
Yes (37) | 1.00 | 0.94 | 0.64 | 0.49 | 0.75 | 0.88 | 0.76 | 0.74 | 0.82 | 0.59 | 0.84 | 0.92 | 0.91 | 0.96 | |
p-value* | 0.262 | 0.128 | 0.696 | 0.775 | 0.971 | 0.497 | 0.355 | 0.685 | 0.913 | 0.225 | 0.055 | 0.054 | 0.069 | 0.061 | |
Digoxin | No (169) | 1.00 | 0.94 | 0.62 | 0.48 | 0.74 | 0.89 | 0.75 | 0.75 | 0.82 | 0.66 | 0.87 | 0.92 | 0.89 | 0.94 |
Yes (11) | 1.00 | 0.91 | 0.59 | 0.45 | 0.52 | 0.71 | 0.71 | 0.60 | 0.63 | 0.52 | 0.80 | 0.92 | 0.84 | 0.91 | |
p-value* | 0.894 | 0.130 | 0.475 | 0.307 | 0.087 | 0.044 | 0.605 | 0.093 | 0.311 | 0.045 | 0.063 | 0.565 | 0.521 | 0.341 | |
Nitrates | No (84) | 1.00 | 0.93 | 0.61 | 0.48 | 0.69 | 0.88 | 0.72 | 0.74 | 0.80 | 0.63 | 0.87 | 0.92 | 0.88 | 0.94 |
Yes (96) | 1.00 | 0.94 | 0.63 | 0.49 | 0.75 | 0.89 | 0.76 | 0.75 | 0.83 | 0.69 | 0.87 | 0.92 | 0.88 | 0.94 | |
p-value* | 0.878 | 0.706 | 0.295 | 0.408 | 0.230 | 0.272 | 0.184 | 0.760 | 0.458 | 0.066 | 0.891 | 0.730 | 0.878 | 0.918 | |
Aspirin | No (42) | 1.00 | 0.93 | 0.60 | 0.45 | 0.69 | 0.92 | 0.77 | 0.74 | 0.81 | 0.68 | 0.89 | 0.93 | 0.88 | 0.96 |
Yes (136) | 1.00 | 0.94 | 0.63 | 0.49 | 0.74 | 0.89 | 0.75 | 0.75 | 0.82 | 0.66 | 0.87 | 0.92 | 0.88 | 0.94 | |
p-value* | 0.590 | 0.509 | 0.044 | 0.044 | 0.666 | 0.902 | 0.363 | 0.706 | 0.716 | 0.683 | 0.599 | 0.194 | 0.930 | 0.007 | |
Clopidogrel | No (79) | 1.00 | 0.94 | 0.61 | 0.48 | 0.74 | 0.90 | 0.75 | 0.76 | 0.79 | 0.63 | 0.87 | 0.92 | 0.88 | 0.94 |
Yes (101) | 1.00 | 0.93 | 0.63 | 0.48 | 0.73 | 0.88 | 0.76 | 0.74 | 0.84 | 0.67 | 0.86 | 0.92 | 0.89 | 0.94 | |
p-value* | 0.156 | 0.535 | 0.100 | 0.380 | 0.953 | 0.871 | 0.775 | 0.985 | 0.256 | 0.768 | 0.971 | 0.999 | 0.544 | 0.573 | |
Warfarin | No (175) | 1.00 | 0.94 | 0.62 | 0.48 | 0.74 | 0.89 | 0.75 | 0.75 | 0.82 | 0.66 | 0.87 | 0.92 | 0.88 | 0.94 |
Yes (5) | 1.00 | 0.93 | 0.64 | 0.47 | 0.72 | 0.77 | 0.66 | 0.63 | 0.78 | 0.54 | 0.89 | 0.91 | 1.00 | 0.93 | |
p-value* | 0.521 | 0.386 | 0.895 | 0.989 | 0.923 | 0.646 | 0.743 | 0.844 | 0.297 | 0.817 | 0.489 | 0.505 | 0.212 | 0.920 | |
Statin | No (19) | 1.00 | 0.94 | 0.58 | 0.45 | 0.73 | 0.93 | 0.84 | 0.81 | 0.84 | 0.64 | 0.87 | 0.91 | 0.93 | 0.95 |
Yes (161) | 1.00 | 0.94 | 0.62 | 0.48 | 0.74 | 0.88 | 0.75 | 0.74 | 0.81 | 0.66 | 0.87 | 0.92 | 0.88 | 0.94 | |
p-value* | 0.510 | 0.716 | 0.209 | 0.131 | 0.750 | 0.594 | 0.121 | 0.228 | 0.914 | 0.696 | 0.874 | 0.710 | 0.658 | 0.325 | |
Antacids | No (119) | 1.00 | 0.94 | 0.63 | 0.49 | 0.74 | 0.91 | 0.76 | 0.76 | 0.84 | 0.66 | 0.87 | 0.92 | 0.89 | 0.94 |
Yes (61) | 1.00 | 0.93 | 0.61 | 0.47 | 0.69 | 0.88 | 0.73 | 0.73 | 0.79 | 0.64 | 0.86 | 0.92 | 0.85 | 0.94 | |
p-value* | 0.959 | 0.525 | 0.624 | 0.669 | 0.515 | 0.333 | 0.226 | 0.328 | 0.354 | 0.757 | 0.824 | 0.364 | 0.072 | 0.341 |