Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner.

Abstract

Statins are widely prescribed to lower plasma low-density lipoprotein (LDL) cholesterol levels. They also modestly reduce plasma triglyceride (TG), an independent cardiovascular disease risk factor, in most people. The mechanism and inter-individual variability of TG statin response is poorly understood. We measured statin-induced gene expression changes in lymphoblastoid cell lines derived from 150 participants of a simvastatin clinical trial and identified 23 genes (false discovery rate, FDR=15%) with expression changes correlated with plasma TG response. The correlation of insulin-induced gene 1 (INSIG1) expression changes with TG response (rho=0.32, q=0.11) was driven by men (interaction P=0.0055). rs73161338 was associated with INSIG1 expression changes (P=5.4 × 10-5) and TG response in two statin clinical trials (P=0.0048), predominantly in men. A combined model including INSIG1 expression level and splicing changes accounted for 29.5% of plasma TG statin response variance in men (P=5.6 × 10-6). Our results suggest that INSIG1 variation may contribute to statin-induced changes in plasma TG in a sex-specific manner.

• Authors: E Theusch, K Kim, K Stevens, J D Smith, Y-D I Chen, J I Rotter, D A Nickerson, M W Medina
• Journal: The pharmacogenomics journal (Pharmacogenomics J) Vol. 17 Issue 3 Pg. 222-229 (06 2017) ISSN: 1473-1150 [Electronic] United States
• PMID: 26927283 (Publication Type: Controlled Clinical Trial, Journal Article)

Chemical References

• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• INSIG1 protein, human
• Intracellular Signaling Peptides and Proteins
• Membrane Proteins
• Triglycerides
• Simvastatin

Topics

• Adult
• Aged
• Cell Line
• Dyslipidemias (blood, diagnosis, drug therapy, genetics)
• Female
• Gene Expression Regulation
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Intracellular Signaling Peptides and Proteins (genetics, metabolism)
• Lymphocytes (drug effects, metabolism)
• Male
• Membrane Proteins (genetics, metabolism)
• Middle Aged
• Pharmacogenetics
• Pharmacogenomic Variants
• Sex Factors
• Simvastatin (therapeutic use)
• Treatment Outcome
• Triglycerides (blood)