Epigenetic Profiling of Type 2 Diabetes Mellitus: An Epigenome-Wide Association Study of DNA Methylation in the Korean Genome and Epidemiology Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Participants and Data Source
2.2. Study Design
2.3. Data Preprocessing and Adjustment of Confounding Effects
2.4. Identification of DMPs
2.5. Identification of DMRs
2.6. Statistical Analyses
3. Results
3.1. Clinical Characteristics of the Study Participants
3.2. Identification of DMPs
3.3. Correlation between Methylation Levels of Top DMPs and Glycemic Markers (FPG and HbA1c)
3.4. Identification of DMRs
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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KoGES Cohort (n = 1134) | Normal (n = 887) | T2DM (n = 247) | p Value a | ||||
---|---|---|---|---|---|---|---|
Mean | SD | n | Mean | SD | n | ||
Sex (% male) | 50.20 | 887 | 57.50 | 247 | - | ||
Age (years) | 57.77 | 8.38 | 887 | 62.45 | 8.22 | 247 | *** |
BMI (kg/m2) | 23.64 | 2.77 | 887 | 25.31 | 2.79 | 247 | *** |
Smoking habit (%) | 37.80 | 887 | 47.30 | 247 | - | ||
Fasting glucose (mg/dL) | 89.26 | 5.64 | 887 | 161.05 | 40.97 | 247 | *** |
HbA1c (%) | 5.35 | 0.21 | 887 | 7.56 | 1.05 | 247 | *** |
2-h plasma glucose (mg/dL) | 105.49 | 21.25 | 887 | 261.96 | 58.38 | 56 | *** |
Fasting insulin (µIU/mL) | 7.63 | 3.04 | 887 | 13.57 | 18.69 | 247 | *** |
2-h plasma insulin (µIU/mL) | 28.69 | 27.68 | 887 | 36.68 | 29.04 | 56 | *** |
Newly detected DM (n, %) | 215, 87.0 | 247 | - | ||||
DM treatment (n, %) | 191, 88.8 | 215 | - | ||||
Oral DM medication (n, %) | 180, 83.7 | 215 | - | ||||
Insulin treatment, (n, %) | 20, 9.3 | 215 | - | ||||
BUN (mg/dL) | 15.26 | 3.94 | 887 | 16.43 | 5.89 | 247 | * |
Creatinine (mg/dL) | 0.93 | 0.15 | 887 | 0.99 | 0.38 | 247 | * |
AST(SGOT) (IU/L) | 25.28 | 9.19 | 887 | 26.47 | 11.88 | 247 | n.s. |
ALT(SGPT) (IU/L) | 22.16 | 12.60 | 886 | 27.90 | 16.19 | 247 | *** |
Total Cholesterol (mg/dL) | 191.87 | 32.92 | 887 | 188.01 | 36.08 | 247 | n.s. |
HDL-Cholesterol (mg/dL) | 44.68 | 11.50 | 887 | 39.51 | 8.56 | 247 | *** |
Triglyceride (mg/dL) | 123.48 | 73.37 | 887 | 181.91 | 112.83 | 247 | *** |
hs-CRP (mg/L) | 1.33 | 3.81 | 887 | 2.12 | 4.96 | 247 | n.s. |
W.B.C. blood (Thous/uL) | 5.22 | 1.35 | 887 | 6.13 | 1.59 | 247 | *** |
R.B.C. blood (Mil/uL) | 4.43 | 0.42 | 887 | 4.46 | 0.46 | 247 | n.s. |
Hemoglobin (Hb) (g/dL) | 13.70 | 1.38 | 887 | 13.73 | 1.49 | 247 | n.s. |
Hematocrit (Hct) (%) | 41.17 | 3.84 | 887 | 41.06 | 4.23 | 247 | n.s. |
Platelet (Thous/uL) | 255.22 | 60.11 | 887 | 255.35 | 66.94 | 247 | n.s. |
Probe | Delta-Beta | p-Value | Adj. p-Value | CHR | MAPINFO | Gene | Feature | cgi | Methylation |
---|---|---|---|---|---|---|---|---|---|
cg19693031 | −0.058 | 2.95 × 10−49 | 2.13 × 10−43 | 1 | 145441552 | TXNIP | 3′UTR | opensea | hypo |
cg26974062 | −0.022 | 2.76 × 10−36 | 9.97 × 10−31 | 1 | 145440734 | TXNIP | Body | opensea | hypo |
cg26823705 | −0.029 | 3.22 × 10−23 | 5.82 × 10−18 | 1 | 145435523 | NBPF20 | Body | opensea | hypo |
cg04816311 | 0.021 | 2.34 × 10−20 | 2.42 × 10−15 | 7 | 1066650 | C7orf50 | Body | shore | hyper |
cg17075888 | −0.033 | 2.52 × 10−19 | 2.03 × 10−14 | 7 | 95225339 | PDK4 | Body | shore | hypo |
cg16740586 | 0.026 | 3.05 × 10−18 | 2.21 × 10−13 | 21 | 43655919 | ABCG1 | Body | shore | hyper |
cg02841972 | −0.021 | 1.90 × 10−15 | 1.06 × 10−10 | 2 | 10176151 | IGR | opensea | hypo | |
cg19750657 | 0.025 | 4.10 × 10−15 | 1.98 × 10−10 | 13 | 38935967 | UFM1 | 3′UTR | opensea | hyper |
cg10217853 | −0.037 | 3.99 × 10−14 | 1.70 × 10−9 | 15 | 98505199 | ARRDC4 | Body | shore | hypo |
cg00683922 | 0.021 | 4.66 × 10−14 | 1.87 × 10−9 | 1 | 207242569 | PFKFB2 | Body | opensea | hyper |
Chromosome | Start | End | Width | p Value | p Value Area | Gene | |
---|---|---|---|---|---|---|---|
DMR_1 | chr6 | 32063114 | 32065211 | 2097 | 0 | 0.00040626 | TNXB |
DMR_2 | chr6 | 30038910 | 30039600 | 690 | 0.0002208 | 0.00106864 | RNF39 |
DMR_3 | chr5 | 135415693 | 135416613 | 920 | 0.0006271 | 0.002040131 | MIR886 |
DMR_4 | chr10 | 530635 | 531584 | 949 | 0.0011923 | 0.003170594 | DIP2C |
DMR_5 | chr1 | 153599479 | 153600156 | 677 | 0.0018193 | 0.004265729 | S100A13 |
DMR_6 | chr6 | 29648161 | 29649024 | 863 | 0.002049 | 0.010306638 | |
DMR_7 | chr6 | 33047944 | 33048879 | 935 | 0.0022698 | 0.005581658 | HLA-DPB1 |
DMR_8 | chr6 | 31691354 | 31692152 | 798 | 0.0024464 | 0.017168898 | C6orf25 |
DMR_9 | chr6 | 31275551 | 31275881 | 330 | 0.0026937 | 0.006924082 | |
DMR_10 | chr16 | 875257 | 875626 | 369 | 0.0026672 | 0.037163952 |
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Seo, H.; Park, J.-H.; Hwang, J.-T.; Choi, H.-K.; Park, S.-H.; Lee, J. Epigenetic Profiling of Type 2 Diabetes Mellitus: An Epigenome-Wide Association Study of DNA Methylation in the Korean Genome and Epidemiology Study. Genes 2023, 14, 2207. https://doi.org/10.3390/genes14122207
Seo H, Park J-H, Hwang J-T, Choi H-K, Park S-H, Lee J. Epigenetic Profiling of Type 2 Diabetes Mellitus: An Epigenome-Wide Association Study of DNA Methylation in the Korean Genome and Epidemiology Study. Genes. 2023; 14(12):2207. https://doi.org/10.3390/genes14122207
Chicago/Turabian StyleSeo, Hyein, Jae-Ho Park, Jin-Taek Hwang, Hyo-Kyoung Choi, Soo-Hyun Park, and Jangho Lee. 2023. "Epigenetic Profiling of Type 2 Diabetes Mellitus: An Epigenome-Wide Association Study of DNA Methylation in the Korean Genome and Epidemiology Study" Genes 14, no. 12: 2207. https://doi.org/10.3390/genes14122207
APA StyleSeo, H., Park, J.-H., Hwang, J.-T., Choi, H.-K., Park, S.-H., & Lee, J. (2023). Epigenetic Profiling of Type 2 Diabetes Mellitus: An Epigenome-Wide Association Study of DNA Methylation in the Korean Genome and Epidemiology Study. Genes, 14(12), 2207. https://doi.org/10.3390/genes14122207