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Table 4 Excerpt of NAFLD associated methylation changes in genes involved in drug metabolism and disposition

From: A targeted analysis reveals relevant shifts in the methylation and transcription of genes responsible for bile acid homeostasis and drug metabolism in non-alcoholic fatty liver disease

 

Discovery Group (n = 74)b

Validation Cohort (n = 54)c

CpG-sites

Healthy vs NAFLD&NASH

Fibrosis stage

Steatosis stage

Gene

Total

Sign.

Sign. (%)a

Illumina ID

Coef.

p

p (FDR)

Coef.

p

Coef.

p

UGT1A1

2

2

100 %

cg19146119

4.66E-02

8.71E-03

1.97E-02

8.02E-02

4.69E-04

-

ns

    

cg07823755

-1.34E-02

1.18E-02

2.57E-02

-1.26E-02

1.41E-02

-

ns

UGT1A4

5

4

80 %

cg04437648

8.11E-02

5.65E-05

1.63E-03

8.83E-02

2.69E-05

-

ns

    

cg05313279

5.12E-02

5.58E-03

1.37E-02

8.79E-02

1.07E-04

-

ns

    

cg02234120

-3.48E-02

2.15E-04

1.93E-03

-3.02E-02

1.69E-03

-

ns

    

cg05141602

-3.23E-02

3.00E-04

2.09E-03

-2.01E-02

4.28E-02

-

ns

CYP1A2

3

2

67 %

cg11473616

6.52E-02

6.09E-04

2.82E-03

7.37E-02

3.87E-04

-

ns

    

cg04968473

5.22E-02

1.54E-02

3.22E-02

8.93E-02

8.76E-04

-

ns

SLCO2B1

9

6

67 %

cg12537437

7.04E-02

9.27E-05

1.63E-03

8.53E-02

3.17E-05

-

ns

    

cg25367084

6.36E-02

3.09E-04

2.09E-03

7.40E-02

4.99E-05

-

ns

    

cg23577865

3.92E-02

7.32E-04

3.21E-03

4.27E-02

6.23E-04

-

ns

    

cg20358275

3.49E-02

6.06E-03

1.47E-02

4.65E-02

5.81E-04

-

ns

    

cg15751948

6.04E-02

1.06E-04

1.64E-03

4.73E-02

7.48E-03

-

ns

    

cg18589858

-1.81E-02

6.54E-03

1.53E-02

-2.77E-02

3.31E-03

-

ns

ABCC2

5

3

60 %

cg17044311

7.22E-02

1.01E-04

1.64E-03

7.84E-02

3.55E-04

-

ns

    

cg14947634

7.21E-02

2.19E-04

1.93E-03

7.08E-02

9.22E-04

-

ns

    

cg09448875

6.81E-02

1.87E-04

1.88E-03

6.60E-02

1.74E-03

-

ns

CYP2C19

6

3

50 %

cg00051662

8.55E-02

6.29E-03

1.49E-02

1.59E-01

1.06E-05

-

ns

    

cg16227251

6.22E-02

5.35E-04

2.73E-03

7.07E-02

6.18E-03

-

ns

    

cg04189838

7.22E-02

2.41E-02

4.95E-02

1.71E-01

1.02E-05

-

ns

UGT2B7

2

1

50 %

cg25583503

5.54E-02

3.16E-04

2.09E-03

6.47E-02

1.47E-03

-

ns

SULT1A1

7

3

43 %

cg01378222

6.76E-02

2.55E-04

1.98E-03

1.13E-01

1.55E-04

-

ns

    

cg09685060

4.34E-02

3.10E-03

8.53E-03

5.18E-02

1.14E-04

-

ns

    

cg08008286

5.22E-02

2.82E-04

2.03E-03

4.89E-02

2.73E-02

-

ns

SLC47A1

15

6

40 %

cg08895056

3.73E-02

3.82E-03

1.01E-02

7.57E-02

2.48E-05

-

ns

    

cg10718608

2.85E-02

7.89E-03

1.80E-02

5.52E-02

4.48E-04

-

ns

    

cg01530032

5.36E-02

9.66E-04

3.93E-03

1.08E-01

2.37E-06

-

ns

    

cg12133118

3.28E-02

1.99E-03

6.36E-03

4.65E-02

4.65E-04

-

ns

    

cg24151087

1.52E-02

1.86E-02

3.84E-02

2.03E-02

5.65E-03

-

ns

    

cg15014549

6.87E-03

2.15E-03

6.76E-03

1.78E-02

2.40E-02

-

ns

CYP2B6

8

3

38 %

cg19756068

5.45E-02

1.20E-04

1.64E-03

4.51E-02

3.04E-03

-

ns

    

cg10322876

4.75E-02

1.38E-03

5.10E-03

4.99E-02

1.79E-03

-

ns

    

cg08852641

-5.57E-02

2.83E-05

1.63E-03

-5.09E-02

2.58E-04

-

ns

CYP1A1

17

6

35 %

cg12101586

6.63E-02

1.92E-05

1.63E-03

1.16E-01

1.62E-06

-

ns

    

cg13570656

7.61E-02

3.93E-05

1.63E-03

1.45E-01

9.83E-06

-

ns

    

cg00213123

5.41E-02

8.07E-05

1.63E-03

1.01E-01

7.50E-06

-

ns

    

cg26516004

7.00E-02

8.42E-05

1.63E-03

1.41E-01

1.19E-06

-

ns

    

cg17852385

6.24E-02

9.05E-05

1.63E-03

1.47E-01

9.82E-06

-

ns

    

cg11924019

4.63E-02

4.57E-04

2.53E-03

9.71E-02

4.93E-05

-

ns

NR2B1

9

1

11 %

cg14651936

-2.38E-02

2.95E-03

8.23E-03

-3.25E-02

5.67E-05

-

ns

GSTP1

10

1

10 %

cg06928838

-5.34E-02

2.96E-03

8.23E-03

-8.12E-02

3.67E-04

-

ns

  1. The full results are shown in (Additional file 1: Table S1). Shown here are only the genes, where methylation was later associated with transcriptional changes (see Table 6)
  2. - no coefficient given for non significant results, n number, ns not significant, coef coefficient, FDR false discovery rate
  3. aPercentage of differentially methylated CpG sites in NAFLD within the TSS1500 interval as confirmed in two cohorts. Order of genes in the list follows the percentage of differentially methylated CpG sites within the TSS1500
  4. bThe discovery cohort is composed of liver healthy and NAFLD patients. Performance of multiple linear regression analyses investigating the association between methylation state of gene associated individuals CpG sites and hepatic disease state. Listed are raw p-values and false discovery (FDR) corrected p-values
  5. cThe validation cohort is composed of NAFLD patients with different stages of steatosis and fibrosis. Performance of multiple linear regression analyses investigating the association between methylation state of gene associated individuals CpG sites and severity of fibrosis and steatotis, respectively. Listed are raw p-values and FDR corrected p-values