Hepatic transcriptomic signatures of statin treatment are associated with impaired glucose homeostasis in severely obese patients

Table 3 Pathway enrichment analysis of statin-dysregulated genes

Pathway (1) or Disease (2) or Regulator (3)	P value	Prediction	Activation Z-score	# Genes
1. Superpathway of cholesterol biosynthesis	1.2 × 10⁻⁴⁰	increased	4.36	19
1. Fatty acid metabolism	2.5 × 10⁻⁰⁹	increased	1.82	18
1. LXR/RXR signaling	2.3 × 10⁻⁰⁸	increased	1.43	8
1. AMPK signaling	9.9 × 10⁻⁰³	decreased	−1.26	4
2. Metabolic disease	9.6 × 10^{− 08}		n.a.	31
2. Insulin resistance	6.9 × 10⁻⁰⁶		n.a.	10
2. Type II diabetes mellitus	1.3 × 10⁻⁰³		n.a.	15
3. SREBF1	1.5 × 10⁻³⁴	activated	4.64	29
3. SREBF2	1.3 × 10⁻⁵⁶	activated	4.74	31
3. SCAP	3.4 × 10⁻⁵²	activated	4.84	27
3. INSIG1	1.3 × 10⁻⁴⁰	inhibited	−3.77	26

Main enriched metabolic and signaling pathways (1), disease processes (2) and regulators (3) modulated by statin treatment in the propensity score-matched patient cohort (n = 314) are shown. The analysis was performed using the Ingenuity Pathway Analysis (IPA) using a list of 98 statin-regulated genes (see Additional file 1: Table S2). The total number of statin-regulated genes assigned to each pathway or disease process is given under the “# genes” column. For regulators (3), the number of downstream target genes is given (all corresponding gene symbols are listed in Additional file 1: Table S4). The Z-score indicates the match between observed and predicted up- or downregulation patterns. Abbreviations: LXR/RXR liver X receptor/retinoid X receptor, AMPK AMP-activated protein kinase, SREBF sterol regulatory element-binding factor, SCAP SREBP-cleavage activating protein, INSIG1 insulin induced gene-1, n.a. no molecular activity prediction available

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