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Table 1 Individual CpG sites in metformin transporter genes that exhibit differential DNA methylation in human liver according to diabetes medication and non-diabetic subjects (n = 93)

From: Diabetes medication associates with DNA methylation of metformin transporter genes in the human liver

Probe ID Chr Position Gene region Non-diabetics (n = 60) No medication (n = 3) Metformin (n = 20) Insulin + Metformin (n = 10) P-ANCOVA q value
SLC22A1
 cg13434757 6 160541976 TSS1500 52.0 ± 0.8 56.0 ± 3.5 48.8 ± 1.3a 56.2 ± 1.9a, b 0.010 0.022
 cg05314142 6 160542711 TSS200 41.7 ± 0.7 43.2 ± 3.3 38.9 ± 1.2 46.3 ± 1.7a, b 0.009 0.022
 cg24864413 6 160542732 TSS200 40.3 ± 0.5 44.5 ± 2.3b 39.5 ± 0.9 47.3 ± 1.2a, b <0.0001 < 0.0001
 cg22416916 6 160542770 TSS200 36.6 ± 0.5 39.5 ± 2.1 35.2 ± 0.8 40.7 ± 1.1a, b 0.002 0.013
 cg13466809 6 160542944 1stExon;5’UTR 35.5 ± 0.4 36.5 ± 2.0 34.3 ± 0.7 39.0 ± 1.1a, b 0.007 0.022
 cg27292431 6 160543261 1stExon 43.2 ± 0.6 46.9 ± 2.9 42.1 ± 1.2 48.4 ± 1.5a, b 0.008 0.022
 Average DNA methylation (13 CpG sites) 56.5 ± 0.2 58.8 ± 1.1a, b 55.7 ± 0.4 58.8 ± 0.6a, b 0.0002  
 DNA methylation promoter region : TSS1500 and TSS200 (4 CpG sites) 42.7 ± 0.5 45.8 ± 2.3b 40.6 ± 0.8a 47.6 ± 1.2a, b 0.0001  
SLC22A3
 cg22117918 6 160769114 TSS1500 8.3 ± 0.2 9.1 ± 0.9 7.9 ± 0.3 9.7 ± 0.5a, b 0.033 0.138
 cg25313204 6 160768801 TSS1500 42.9 ± 0.6 48.2 ± 2.8 42.9 ± 1.0 47.8 ± 1.5a, b 0.014 0.107
 cg06295784 6 160771074 Body 40.7 ± 0.5 44.3 ± 2.5 39.6 ± 10.9 44.8 ± 1.3a, b 0.012 0.107
 cg13280882 6 160771574 Body 77.3 ± 1.4 91.9 ± 6.4a, b 77.3 ± 2.4 85.9 ± 3.4a, b 0.033 0.138
 cg11696576 6 160815734 Body 45.1 ± 0.6 52.0 ± 2.7a, b 42.3 ± 1.0a 49.2 ± 1.4a, b 0.0002 0.005
 cg04794858 6 16086035 Body 91.3 ± 0.3 89.6 ± 1.3 90.9 ± 0.5 89.0 ± 0.7a, b 0.036 0.138
 Average DNA methylation (23 CpG sites) 56.0 ± 0.2 57.9 ± 0.8a, b 55.7 ± 0.3 56.9 ± 0.4b 0.033  
 DNA methylation promoter region: TSS1500 and TSS200 (5 CpG sites) 31.2 ± 0.2 32.8 ± 0.9b 30.8 ± 0.3 32.6 ± 0.5a, b 0.013  
SLC47A1
 cg01530032 17 19435805 TSS1500 31.7 ± 0.7 38.5 ± 3.0a, b 30.6 ± 1.1 39.7 ± 1.6a, b 0.0001 0.001
 cg25387636 17 19436896 TSS1500 7.4 ± 0.2 8.0 ± 1.1 6.3 ± 0.4a 8.5 ± 0.6b 0.019 0.057
 cg15971010 17 19436900 TSS1500 10.1 ± 0.3 11.2 ± 1.5 8.6 ± 0.5a 12.0 ± 0.8a, b 0.007 0.028
 cg15014549 17 19437003 TSS200 3.7 ± 0.7 3.7 ± 0.3 3.8 ± 0.1 4.4 ± 0.2a, b 0.007 0.028
 cg07829432 17 19437013 TSS200 3.8 ± 0.1 4.7 ± 0.4 3.8 ± 0.2 5.2 ± 0.2a, b <0.0001 < 0.0001
 cg20930201 17 19437691 Body 7.7 ± 0.2 9.2 ± 0.9b 6.7 ± 0.3a 9.1 ± 0.5a, b 0.0009 0.007
 cg26959235 17 19437889 Body 12.7 ± 0.2 11.9 ± 1.1 12.7 ± 0.4 10.8 ± 0.6a, b 0.033 0.086
 cg24151087 17 19450271 Body 9.9 ± 0.2 10.5 ± 1.2 9.8 ± 0.4 12.1 ± 0.6a, b 0.018 0.057
 cg16887170 17 19451180 Body 84.0 ± 0.4 83.3 ± 1.8 81.7 ± 0.7a 83.0 ± 0.9 0.036 0.086
 cg12550399 17 19482275 3′ UTR 64.2 ± 0.8 67.0 ± 3.6 62.8 ± 1.3 71.9 ± 1.9a, b 0.002 0.011
 Average DNA methylation (24 CpG sites) 33.1 ± 0.1 34.0 ± 0.6b 32.7 ± 0.2 34.5 ± 0.3a, b 0.0001  
 DNA methylation promoter region: TSS1500 and TSS200 (11 CpG sites) 12.2 ± 0.2 13.2 ± 0.8 11.6 ± 0.3 14.3 ± 0.4a, b <0.0001  
  1. Data are shown as mean ± SEM. All data is adjusted for age, sex, and NASH. Post-hoc analysis is used for comparisons between groups after ANCOVA. q values are based on false discovery rate (FDR) tests after ANCOVA
  2. a P < 0.05 compared to non-diabetic subjects
  3. b P < 0.05 compared to metformin treatment