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

Table 5 Methylation/transcription correlations of genes involved in bile acid homeostasis in NAFLD

						Pearson correlation analyses^d
	CpG-sites			Robust linear regression (n = 50)^b		SS & NASH (n = 20)		Controls (n = 30)
Gene	Total	Sign.^a	p (binomial)	Coef.	p	Coef.	p	Coef.	p
Hypermethylated targets
ABCB11	3	2	7.25E-03	-	ns	-	ns	-	ns
ABCC2	5	3	1.16E-03	-	ns	-	ns	-	ns
ABCG5	12	11	5.59E-14	-	ns	-	ns	-	ns
ATP8B1	9	1	ns	-	ns	-0.52	1.77E-02	-	ns
CYP27A1	5	1	ns	-0.70	4.54E-05	-	ns	-0.57	9.50E-04
CYP7B1	12	4	2.24E-03	-	ns	-	ns	-	ns
CYP8B1	6	5	1.80E-06	-	ns	-	ns	-	ns
*EPHX1*	13	9	1.16E-09	-0.50	5.99E-03	-	ns	-	ns
FGFR4	12	2	ns	-0.45	8.05E-05	-	ns	-0.39	3.21E-02
HNF1A	8	8	3.91E-11	-	ns	-	ns	-	ns
NR0B2	5	3	1.16E-03	-	ns	-	ns	-	ns
NR1H4	4	3	4.81E-04	-	ns	-	ns	-	ns
NR1I3	4	3	4.81E-04	-	ns	-	ns	-	ns
NR2A1	18	15	2.16E-17	-	ns	-	ns	-	ns
*SLC51A*	7	6	1.05E-07	-0.25	2.37E-02	-	ns	-	ns
*SLC10A1*	6	3	2.23E-03	-11.00	3.67E-08 ^c	-	ns	-	ns
*SLC27A5*	13	5	2.87E-04	-0.27	1.42E-02	-	ns	-	ns
*SLCO2B1*	9	5	3.32E-05	-0.38	1.41E-03	-	ns	-	ns
UGT2B11	1	1	ns	-	ns	0.56	9.60E-03	-	ns
Hypomethylated targets
ABCC3	8	1	ns	-	ns	0.46	3.94E-02	-	ns
CYP3A4	3	2	7.25E-03	-	ns	-	ns	-	ns
NR1I2	5	2	2.26E-02	-	ns	-	ns	-	ns
NR2B1	9	1	ns	-	ns	-	ns	0.42	2.09E-02
NR5A2	21	2	ns	-	ns	-	ns	-0.44	1.62E-02
SCP2	7	1	ns	-	ns	-0.48	3.15E-02	-	ns
SLCO2B1	9	1	ns	0.26	7.07E-03	-	ns	0.47	8.22E-03

The Table lists genes with NAFLD dependent significant changes in the overall CpG site methylation within the TSS1500 interval after binomial testing and its association to transcriptional changes. Genes showing significant changes in average methylation with significant association to transcription are shown in bold
- no coefficient given for non significant results, n number, ns not significant, coef coefficient, sign. significant
^aNumber of significantly hyper- or hypomethylated CpG sites in discovery and validation cohort. Genes in the list appear according to their alphabetical order
^bRegression analyses studying the association between average methylation in the TSS1500 interval and strength of transcription in the EC cohort. Analyses are taking the strength of fibrosis and steatosis into account
^cRegression analyses under consideration of a fibrosis/expression interaction term
^dPearson’s correlation analyses correlating average methylation state in the TSS1500 interval and strength of transcription in NAFLD and non-NAFLD patients of the EC cohort

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