PHOSPHO1 Gene DNA Methylations are Associated with a Change in HDL-C Response to Simvastatin Treatment.

Current Pharmaceutical Design
Juanlin FanShanqun Jiang

Abstract

Our aim was to detect the effects of DNA methylations in the phosphoethanolamine/ phosphocholine phosphatase (PHOSPHO1) gene on the therapeutic efficacy of simvastatin. We used an extreme sampling approach by selecting 211 individuals from approximately the top and bottom 15% of adjusted lipid-lowering response residuals to simvastatin (n=104 for the high response group and n=107 for the low response group) from a total of 734 subjects with hyperlipidemia. They received a daily oral dose of 20 mg simvastatin for eight consecutive weeks. DNA methylation loci at the PHOSPHO1 gene were measured using high-throughput next-generation sequencing-based sequencing technology. Fasting serum lipids were measured at baseline and after eight weeks of simvastatin treatment. Mean PHOSPHO1 DNA methylation had a significant negative correlation with high-density lipoprotein cholesterol (HDL-C) variation (β=-0.014, P=0.045) in the high response group. After stratifying by body mass index (BMI), the associations between the PHOSPHO1 DNA methylations and the change in HDL-C in response to simvastatin were more significant in obese subjects with a BMI of 25 kg/m2 or higher (β=-0.027, P=0.002). Mean PHOSPHO1 methylation and traditional predictors c...Continue Reading

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Citations

Oct 24, 2020·BMC Biology·Karla J SuchackiColin Farquharson

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