Journal of Southern Medical University ›› 2025, Vol. 45 ›› Issue (9): 1859-1866.doi: 10.12122/j.issn.1673-4254.2025.09.06
Jialie JIN1,2(), Fei WANG1, Liya ZHU1, Xiaojing ZHAO3,4, Jinxin WANG5, Chao ZHU6(
), Rongxi YANG1(
)
Received:
2025-03-21
Online:
2025-09-20
Published:
2025-09-28
Contact:
Chao ZHU, Rongxi YANG
E-mail:jljin@cdc.zj.cn;zhuchaodoctor@163.com;rongxiyang@njmu.edu.cn
Supported by:
Jialie JIN, Fei WANG, Liya ZHU, Xiaojing ZHAO, Jinxin WANG, Chao ZHU, Rongxi YANG. Association between MLPH gene hypermethylation in peripheral blood and coronary heart disease[J]. Journal of Southern Medical University, 2025, 45(9): 1859-1866.
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URL: https://www.j-smu.com/EN/10.12122/j.issn.1673-4254.2025.09.06
Variables | CHD group (n=86) | Control group (n=95) | Z/χ2 | P |
---|---|---|---|---|
Gender [n (%)] | 3.113 | 0.078a | ||
Male | 52 (60.5) | 45 (47.4) | ||
Female | 34 (39.5) | 50 (52.6) | ||
Smoking [n (%)] | 7.983 | 0.005a | ||
Yes | 35 (40.7) | 20 (21.1) | ||
No | 51 (59.3) | 74 (77.9) | ||
Drinking [n (%)] | 0.034 | 0.853a | ||
Yes | 23 (26.7) | 24 (25.3) | ||
No | 63 (73.3) | 70 (73.7) | ||
Hypertension [n (%)] | 6.004 | 0.014a | ||
Yes | 55 (64.0) | 42 (44.2) | ||
No | 31 (36.0) | 50 (52.6) | ||
Diabetes [n (%)] | 4.314 | 0.038a | ||
Yes | 34 (39.5) | 23 (24.2) | ||
No | 52 (60.5) | 69 (72.6) | ||
Age (years) | 65 (57, 73) | 63 (61,68) | -0.364 | 0.716b |
TC (mmol/L) | 3.79 (3.26, 4.41) | 4.21 (3.59, 5.02) | -2.608 | 0.009b |
TG (mmol/L) | 1.33 (0.97, 1.86) | 1.38 (1.06, 1.92) | -0.562 | 0.574b |
HDL-C (mmol/L) | 1.03 (0.86, 1.29) | 1.18 (0.91, 1.41) | -1.829 | 0.067b |
LDL-C (mmol/L) | 2.27 (1.85, 2.76) | 2.64 (2.07, 3.35) | -2.794 | 0.005b |
Tab.1 Baseline data from patients with CHD and normal controls
Variables | CHD group (n=86) | Control group (n=95) | Z/χ2 | P |
---|---|---|---|---|
Gender [n (%)] | 3.113 | 0.078a | ||
Male | 52 (60.5) | 45 (47.4) | ||
Female | 34 (39.5) | 50 (52.6) | ||
Smoking [n (%)] | 7.983 | 0.005a | ||
Yes | 35 (40.7) | 20 (21.1) | ||
No | 51 (59.3) | 74 (77.9) | ||
Drinking [n (%)] | 0.034 | 0.853a | ||
Yes | 23 (26.7) | 24 (25.3) | ||
No | 63 (73.3) | 70 (73.7) | ||
Hypertension [n (%)] | 6.004 | 0.014a | ||
Yes | 55 (64.0) | 42 (44.2) | ||
No | 31 (36.0) | 50 (52.6) | ||
Diabetes [n (%)] | 4.314 | 0.038a | ||
Yes | 34 (39.5) | 23 (24.2) | ||
No | 52 (60.5) | 69 (72.6) | ||
Age (years) | 65 (57, 73) | 63 (61,68) | -0.364 | 0.716b |
TC (mmol/L) | 3.79 (3.26, 4.41) | 4.21 (3.59, 5.02) | -2.608 | 0.009b |
TG (mmol/L) | 1.33 (0.97, 1.86) | 1.38 (1.06, 1.92) | -0.562 | 0.574b |
HDL-C (mmol/L) | 1.03 (0.86, 1.29) | 1.18 (0.91, 1.41) | -1.829 | 0.067b |
LDL-C (mmol/L) | 2.27 (1.85, 2.76) | 2.64 (2.07, 3.35) | -2.794 | 0.005b |
CpG sites | CHD group (n=86) | Control group (n=95) | Z | P* |
---|---|---|---|---|
TSSC1_CpG_1 | 0.89 (0.82, 0.95) | 0.85 (0.77, 0.93) | -1.258 | 0.208 |
TSSC1_CpG_6/cg23245316 | 0.43 (0.33, 0.53) | 0.41 (0.32, 0.55) | -0.007 | 0.994 |
TSSC1_CpG_7 | 1.00 (0.98, 1.00) | 1.00 (0.97, 1.00) | -0.389 | 0.697 |
TSSC1_CpG_8 | 0.68 (0.60, 0.77) | 0.67 (0.59, 0.73) | -1.474 | 0.140 |
TSSC1_CpG_12 | 1.00 (0.89, 1.00) | 1.00 (0.91, 1.00) | -0.315 | 0.753 |
TSSC1_CpG_14 | 0.33 (0.26, 0.39) | 0.31 (0.24, 0.39) | -0.942 | 0.346 |
TSSC1_CpG_15 | 0.38 (0.33, 0.50) | 0.42 (0.32, 0.49) | -0.329 | 0.742 |
TSSC1_CpG_16 | 0.96 (0.92, 0.97) | 0.96 (0.93, 0.97) | -0.593 | 0.553 |
TSSC1_CpG_17 | 1.00 (1.00, 1.00) | 1.00 (0.98, 1.00) | -1.629 | 0.103 |
TSSC1_CpG_18 | 0.98 (0.95, 0.99) | 0.99 (0.96, 0.99) | -0.468 | 0.640 |
MLPH_CpG_2.7 | 0.85 (0.81, 0.93) | 0.84 (0.80, 0.90) | -1.715 | 0.086 |
MLPH_CpG_3/cg06639874 | 0.92 (0.84, 0.97) | 0.90 (0.87, 0.94) | -0.657 | 0.511 |
MLPH_CpG_4 | 0.94 (0.89, 0.99) | 0.94 (0.88, 0.96) | -1.410 | 0.159 |
MLPH_CpG_5 | 0.87 (0.82, 0.95) | 0.86 (0.82, 0.90) | -1.763 | 0.078 |
MLPH_CpG_6 | 0.59 (0.37, 0.69) | 0.56 (0.36, 0.67) | -1.217 | 0.224 |
Tab.2 Differences in methylation levels of TSSC1 and MLPH genes between CHD and control groups [M(P25, P75)]
CpG sites | CHD group (n=86) | Control group (n=95) | Z | P* |
---|---|---|---|---|
TSSC1_CpG_1 | 0.89 (0.82, 0.95) | 0.85 (0.77, 0.93) | -1.258 | 0.208 |
TSSC1_CpG_6/cg23245316 | 0.43 (0.33, 0.53) | 0.41 (0.32, 0.55) | -0.007 | 0.994 |
TSSC1_CpG_7 | 1.00 (0.98, 1.00) | 1.00 (0.97, 1.00) | -0.389 | 0.697 |
TSSC1_CpG_8 | 0.68 (0.60, 0.77) | 0.67 (0.59, 0.73) | -1.474 | 0.140 |
TSSC1_CpG_12 | 1.00 (0.89, 1.00) | 1.00 (0.91, 1.00) | -0.315 | 0.753 |
TSSC1_CpG_14 | 0.33 (0.26, 0.39) | 0.31 (0.24, 0.39) | -0.942 | 0.346 |
TSSC1_CpG_15 | 0.38 (0.33, 0.50) | 0.42 (0.32, 0.49) | -0.329 | 0.742 |
TSSC1_CpG_16 | 0.96 (0.92, 0.97) | 0.96 (0.93, 0.97) | -0.593 | 0.553 |
TSSC1_CpG_17 | 1.00 (1.00, 1.00) | 1.00 (0.98, 1.00) | -1.629 | 0.103 |
TSSC1_CpG_18 | 0.98 (0.95, 0.99) | 0.99 (0.96, 0.99) | -0.468 | 0.640 |
MLPH_CpG_2.7 | 0.85 (0.81, 0.93) | 0.84 (0.80, 0.90) | -1.715 | 0.086 |
MLPH_CpG_3/cg06639874 | 0.92 (0.84, 0.97) | 0.90 (0.87, 0.94) | -0.657 | 0.511 |
MLPH_CpG_4 | 0.94 (0.89, 0.99) | 0.94 (0.88, 0.96) | -1.410 | 0.159 |
MLPH_CpG_5 | 0.87 (0.82, 0.95) | 0.86 (0.82, 0.90) | -1.763 | 0.078 |
MLPH_CpG_6 | 0.59 (0.37, 0.69) | 0.56 (0.36, 0.67) | -1.217 | 0.224 |
Fig.1 Correlation of methylation levels of TSSC1 and MLPH genes with age and male. A: Heat map of the correlation between age and methylation levels. B: Scatter plot of the correlation between MLPH_CpG_4 methylation level and age in CHD cases. C: Scatter plot of the correlation between MLPH_CpG_4 methylation level and age in control group. D: Bubble chart of the correlation between male gender and methylation levels.
CpG sites | Age<65 years (n=101) | Age≥65 year (n=80) | |||||
---|---|---|---|---|---|---|---|
CHD (n=41) | Control (n=0) | P* | CHD (n=45) | Control (n=35) | P * | ||
TSSC1_CpG_1 | 0.92 (0.82, 0.95) | 0.85 (0.76, 0.93) | 0.151 | 0.89 (0.79, 0.95) | 0.86 (0.76, 0.95) | 0.725 | |
TSSC1_CpG_6/cg23245316 | 0.42 (0.29, 0.53) | 0.40 (0.29, 0.55) | 0.730 | 0.44 (0.34, 0.54) | 0.45 (0.36, 0.58) | 0.470 | |
TSSC1_CpG_7 | 1.00 (0.97, 1.00) | 1.00 (0.97, 1.00) | 0.888 | 1.00 (0.98, 1.00) | 1.00 (0.96, 1.00) | 0.419 | |
TSSC1_CpG_8 | 0.68 (0.56, 0.76) | 0.68 (0.59, 0.73) | 0.921 | 0.69 (0.62, 0.77) | 0.66 (0.59, 0.73) | 0.233 | |
TSSC1_CpG_12 | 1.00 (0.90, 1.00) | 1.00 (0.89, 1.00) | 0.687 | 1.00 (0.89, 1.00) | 1.00 (0.93, 1.00) | 0.352 | |
TSSC1_CpG_14 | 0.33 (0.25, 0.39) | 0.31 (0.25, 0.38) | 0.888 | 0.34 (0.29, 0.42) | 0.32 (0.21, 0.43) | 0.384 | |
TSSC1_CpG_15 | 0.37 (0.31, 0.51) | 0.42 (0.31, 0.47) | 0.969 | 0.40 (0.33, 0.50) | 0.42 (0.35, 0.50) | 0.507 | |
TSSC1_CpG_16 | 0.96 (0.94, 0.97) | 0.96 (0.92, 0.97) | 1.000 | 0.96 (0.90, 0.97) | 0.96 (0.93, 0.97) | 0.405 | |
TSSC1_CpG_17 | 1.00 (1.00, 1.00) | 1.00 (0.99, 1.00) | 0.701 | 1.00 (1.00, 1.00) | 1.00 (0.98, 1.00) | 0.051 | |
TSSC1_CpG_18 | 0.98 (0.94, 0.99) | 0.99 (0.95, 0.99) | 0.320 | 0.99 (0.96, 0.99) | 0.98 (0.96, 0.99) | 0.744 | |
MLPH_CpG_2.7 | 0.86 (0.83, 0.94) | 0.83 (0.80, 0.89) | 0.014 | 0.85 (0.80, 0.91) | 0.85 (0.79, 0.93) | 0.941 | |
MLPH_CpG_3/cg06639874 | 0.95 (0.87, 0.98) | 0.91 (0.88, 0.96) | 0.147 | 0.89 (0.82, 0.94) | 0.89 (0.83, 0.93) | 0.930 | |
MLPH_CpG_4 | 0.97 (0.93, 1.00) | 0.93 (0.87, 0.95) | 0.001 | 0.92 (0.86, 0.98) | 0.94 (0.89, 0.97) | 0.187 | |
MLPH_CpG_5 | 0.86 (0.81, 0.95) | 0.86 (0.82, 0.89) | 0.652 | 0.90 (0.84, 0.95) | 0.87 (0.84, 0.91) | 0.104 | |
MLPH_CpG_6 | 0.58 (0.35, 0.71) | 0.55 (0.35, 0.67) | 0.568 | 0.62 (0.41, 0.69) | 0.57 (0.39, 0.66) | 0.284 | |
*The P values were calculated by the Mann-Whitney U test. |
Tab.4 Differences in TSSC1 and MLPH gene methylation between CHD and control groups stratified by age [M (P25,P75)]
CpG sites | Age<65 years (n=101) | Age≥65 year (n=80) | |||||
---|---|---|---|---|---|---|---|
CHD (n=41) | Control (n=0) | P* | CHD (n=45) | Control (n=35) | P * | ||
TSSC1_CpG_1 | 0.92 (0.82, 0.95) | 0.85 (0.76, 0.93) | 0.151 | 0.89 (0.79, 0.95) | 0.86 (0.76, 0.95) | 0.725 | |
TSSC1_CpG_6/cg23245316 | 0.42 (0.29, 0.53) | 0.40 (0.29, 0.55) | 0.730 | 0.44 (0.34, 0.54) | 0.45 (0.36, 0.58) | 0.470 | |
TSSC1_CpG_7 | 1.00 (0.97, 1.00) | 1.00 (0.97, 1.00) | 0.888 | 1.00 (0.98, 1.00) | 1.00 (0.96, 1.00) | 0.419 | |
TSSC1_CpG_8 | 0.68 (0.56, 0.76) | 0.68 (0.59, 0.73) | 0.921 | 0.69 (0.62, 0.77) | 0.66 (0.59, 0.73) | 0.233 | |
TSSC1_CpG_12 | 1.00 (0.90, 1.00) | 1.00 (0.89, 1.00) | 0.687 | 1.00 (0.89, 1.00) | 1.00 (0.93, 1.00) | 0.352 | |
TSSC1_CpG_14 | 0.33 (0.25, 0.39) | 0.31 (0.25, 0.38) | 0.888 | 0.34 (0.29, 0.42) | 0.32 (0.21, 0.43) | 0.384 | |
TSSC1_CpG_15 | 0.37 (0.31, 0.51) | 0.42 (0.31, 0.47) | 0.969 | 0.40 (0.33, 0.50) | 0.42 (0.35, 0.50) | 0.507 | |
TSSC1_CpG_16 | 0.96 (0.94, 0.97) | 0.96 (0.92, 0.97) | 1.000 | 0.96 (0.90, 0.97) | 0.96 (0.93, 0.97) | 0.405 | |
TSSC1_CpG_17 | 1.00 (1.00, 1.00) | 1.00 (0.99, 1.00) | 0.701 | 1.00 (1.00, 1.00) | 1.00 (0.98, 1.00) | 0.051 | |
TSSC1_CpG_18 | 0.98 (0.94, 0.99) | 0.99 (0.95, 0.99) | 0.320 | 0.99 (0.96, 0.99) | 0.98 (0.96, 0.99) | 0.744 | |
MLPH_CpG_2.7 | 0.86 (0.83, 0.94) | 0.83 (0.80, 0.89) | 0.014 | 0.85 (0.80, 0.91) | 0.85 (0.79, 0.93) | 0.941 | |
MLPH_CpG_3/cg06639874 | 0.95 (0.87, 0.98) | 0.91 (0.88, 0.96) | 0.147 | 0.89 (0.82, 0.94) | 0.89 (0.83, 0.93) | 0.930 | |
MLPH_CpG_4 | 0.97 (0.93, 1.00) | 0.93 (0.87, 0.95) | 0.001 | 0.92 (0.86, 0.98) | 0.94 (0.89, 0.97) | 0.187 | |
MLPH_CpG_5 | 0.86 (0.81, 0.95) | 0.86 (0.82, 0.89) | 0.652 | 0.90 (0.84, 0.95) | 0.87 (0.84, 0.91) | 0.104 | |
MLPH_CpG_6 | 0.58 (0.35, 0.71) | 0.55 (0.35, 0.67) | 0.568 | 0.62 (0.41, 0.69) | 0.57 (0.39, 0.66) | 0.284 | |
*The P values were calculated by the Mann-Whitney U test. |
CpG sites | Female (n=84) | Male (n=97) | |||||
---|---|---|---|---|---|---|---|
CHD (n=34) | Control (n=50) | P* | CHD (n = 52) | Control (n = 45) | P* | ||
TSSC1_CpG_1 | 0.90 (0.83, 0.96) | 0.85 (0.75, 0.95) | 0.135 | 0.89 (0.76, 0.95) | 0.86 (0.79, 0.93) | 0.566 | |
TSSC1_CpG_6/cg23245316 | 0.44 (0.33, 0.55) | 0.38 (0.31, 0.48) | 0.160 | 0.43 (0.32, 0.52) | 0.45 (0.35, 0.58) | 0.114 | |
TSSC1_CpG_7 | 1.00 (0.97, 1.00) | 1.00 (0.97, 1.00) | 0.545 | 1.00 (0.98, 1.00) | 1.00 (0.96, 1.00) | 0.298 | |
TSSC1_CpG_8 | 0.74 (0.68, 0.79) | 0.68 (0.59, 0.73) | 0.014 | 0.65 (0.52, 0.72) | 0.66 (0.58, 0.72) | 0.420 | |
TSSC1_CpG_12 | 1.00 (0.91, 1.00) | 1.00 (0.92, 1.00) | 0.467 | 1.00 (0.88, 1.00) | 0.98 (0.90, 1.00) | 0.687 | |
TSSC1_CpG_14 | 0.35 (0.27, 0.41) | 0.33 (0.24, 0.43) | 0.461 | 0.33 (0.25, 0.39) | 0.30 (0.24, 0.36) | 0.349 | |
TSSC1_CpG_15 | 0.43 (0.34, 0.53) | 0.41 (0.31, 0.46) | 0.131 | 0.38 (0.30, 0.46) | 0.44 (0.34, 0.52) | 0.077 | |
TSSC1_CpG_16 | 0.96 (0.90, 0.97) | 0.96 (0.92, 0.97) | 0.447 | 0.96 (0.93, 0.97) | 0.96 (0.93, 0.97) | 0.870 | |
TSSC1_CpG_17 | 1.00 (1.00, 1.00) | 1.00 (0.99, 1.00) | 0.134 | 1.00 (1.00, 1.00) | 1.00 (0.98, 1.00) | 0.290 | |
TSSC1_CpG_18 | 0.98 (0.96, 0.99) | 0.99 (0.96, 0.99) | 0.677 | 0.99 (0.93, 0.99) | 0.99 (0.95, 0.99) | 0.756 | |
MLPH_CpG_2.7 | 0.83 (0.77, 0.89) | 0.84 (0.80, 0.91) | 0.323 | 0.87 (0.83, 0.94) | 0.83 (0.78, 0.88) | 0.004 | |
MLPH_CpG_3/cg06639874 | 0.90 (0.81, 0.95) | 0.91 (0.86, 0.96) | 0.215 | 0.94 (0.86, 0.97) | 0.90 (0.87, 0.92) | 0.044 | |
MLPH_CpG_4 | 0.93 (0.86, 1.00) | 0.93 (0.89, 0.96) | 0.966 | 0.95 (0.90, 0.99) | 0.94 (0.88, 0.96) | 0.090 | |
MLPH_CpG_5 | 0.86 (0.82, 0.93) | 0.85 (0.82, 0.89) | 0.294 | 0.90 (0.83, 0.95) | 0.87 (0.84, 0.91) | 0.228 | |
MLPH_CpG_6 | 0.62 (0.44, 0.69) | 0.49 (0.31, 0.64) | 0.099 | 0.58 (0.34, 0.74) | 0.58 (0.41, 0.68) | 0.981 |
Tab.5 Differences in TSSC1 and MLPH gene methylation between CHD and control groups stratified by sex [M (P25,P75)]
CpG sites | Female (n=84) | Male (n=97) | |||||
---|---|---|---|---|---|---|---|
CHD (n=34) | Control (n=50) | P* | CHD (n = 52) | Control (n = 45) | P* | ||
TSSC1_CpG_1 | 0.90 (0.83, 0.96) | 0.85 (0.75, 0.95) | 0.135 | 0.89 (0.76, 0.95) | 0.86 (0.79, 0.93) | 0.566 | |
TSSC1_CpG_6/cg23245316 | 0.44 (0.33, 0.55) | 0.38 (0.31, 0.48) | 0.160 | 0.43 (0.32, 0.52) | 0.45 (0.35, 0.58) | 0.114 | |
TSSC1_CpG_7 | 1.00 (0.97, 1.00) | 1.00 (0.97, 1.00) | 0.545 | 1.00 (0.98, 1.00) | 1.00 (0.96, 1.00) | 0.298 | |
TSSC1_CpG_8 | 0.74 (0.68, 0.79) | 0.68 (0.59, 0.73) | 0.014 | 0.65 (0.52, 0.72) | 0.66 (0.58, 0.72) | 0.420 | |
TSSC1_CpG_12 | 1.00 (0.91, 1.00) | 1.00 (0.92, 1.00) | 0.467 | 1.00 (0.88, 1.00) | 0.98 (0.90, 1.00) | 0.687 | |
TSSC1_CpG_14 | 0.35 (0.27, 0.41) | 0.33 (0.24, 0.43) | 0.461 | 0.33 (0.25, 0.39) | 0.30 (0.24, 0.36) | 0.349 | |
TSSC1_CpG_15 | 0.43 (0.34, 0.53) | 0.41 (0.31, 0.46) | 0.131 | 0.38 (0.30, 0.46) | 0.44 (0.34, 0.52) | 0.077 | |
TSSC1_CpG_16 | 0.96 (0.90, 0.97) | 0.96 (0.92, 0.97) | 0.447 | 0.96 (0.93, 0.97) | 0.96 (0.93, 0.97) | 0.870 | |
TSSC1_CpG_17 | 1.00 (1.00, 1.00) | 1.00 (0.99, 1.00) | 0.134 | 1.00 (1.00, 1.00) | 1.00 (0.98, 1.00) | 0.290 | |
TSSC1_CpG_18 | 0.98 (0.96, 0.99) | 0.99 (0.96, 0.99) | 0.677 | 0.99 (0.93, 0.99) | 0.99 (0.95, 0.99) | 0.756 | |
MLPH_CpG_2.7 | 0.83 (0.77, 0.89) | 0.84 (0.80, 0.91) | 0.323 | 0.87 (0.83, 0.94) | 0.83 (0.78, 0.88) | 0.004 | |
MLPH_CpG_3/cg06639874 | 0.90 (0.81, 0.95) | 0.91 (0.86, 0.96) | 0.215 | 0.94 (0.86, 0.97) | 0.90 (0.87, 0.92) | 0.044 | |
MLPH_CpG_4 | 0.93 (0.86, 1.00) | 0.93 (0.89, 0.96) | 0.966 | 0.95 (0.90, 0.99) | 0.94 (0.88, 0.96) | 0.090 | |
MLPH_CpG_5 | 0.86 (0.82, 0.93) | 0.85 (0.82, 0.89) | 0.294 | 0.90 (0.83, 0.95) | 0.87 (0.84, 0.91) | 0.228 | |
MLPH_CpG_6 | 0.62 (0.44, 0.69) | 0.49 (0.31, 0.64) | 0.099 | 0.58 (0.34, 0.74) | 0.58 (0.41, 0.68) | 0.981 |
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