ZNF542P is a pseudogene associated with LDL response to simvastatin treatment

Figures

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  Figure 1. Prediction of statin sensitivity in 12 African American high and 14 African American low responders. Area under the curve (AUC) values were calculated from ROC curves of sensitivity vs. 1-specificity as the classification threshold was varied, with (a) the top 100 signature genes derived from six different datasets corrected by different numbers of PCs and (b) varying numbers of signature genes from the 15 PC corrected dataset.

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  Figure 2. Cellular cholesterol ester statin response differs between LCLs from high versus low LDLC statin responders. Intracellular cholesterol esters (CE, panel a) and free cholesterol (FC, panel b) were measured in LCLs from 25 European American high and 24 European American low statin responders after 24 hr incubation with 2 μM simvastatin or control buffer. Two-sided Student’s T-tests were performed to identify significant differences between high and low responders. Individual data points with mean ± s.e.m. are shown.

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  Figure 3. ZNF542P statin response is negatively correlated with intracellular cholesterol ester and plasma LDLC statin responses. Statin-induced changes in ZNF542P expression levels were quantified in 104 European American CAP LCLs after in vitro exposure to 2 μM simvastatin or control buffer. (a) ZNF542P expression changes were tested for correlation with statin induced change in cellular cholesterol ester (CE) quantified in the statin and control treated LCLs from 103 European Americans. Delta cholesterol ester was calculated as the log difference of the statin minus control treated cells. (b) ZNF542P expression levels were quantified by RNA-seq in CAP LCLs from 25 European American LDLC high responders and 25 European American LDLC low responders after 24 hr in vitro incubation with 2 μM simvastatin or control buffer. P-values were calculated using empirical Bayes moderated t-statistics with 5000 permutations to indicate differences in ZNF542P expression changes between high and low responders. For graphical purposes, ZNF542P fold change was estimated as 2^(variance stabilized control-variance stabilized statin) since variance stabilization is roughly a log2 transformation, but the…

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  Figure 4. ZNF542P knock-down alters cellular cholesterol levels. Huh7 cells were reverse transfected with siRNAs targeting ZNF542P or a non-targeting control (NTC), exposed to simvastatin (0.5, 2 or 5 μM) or control buffer for 24 hours, after which cellular cholesterol was quantified, n = 4–12 per treatment condition. Values were normalized to the average of the NTC siRNA control treated cells and shown as mean ± s.e.m.