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Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner
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 unders...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008997/ https://www.ncbi.nlm.nih.gov/pubmed/26927283 http://dx.doi.org/10.1038/tpj.2016.12 |
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author | Theusch, E Kim, K Stevens, K Smith, J D Chen, Y -D I Rotter, J I Nickerson, D A Medina, M W |
author_facet | Theusch, E Kim, K Stevens, K Smith, J D Chen, Y -D I Rotter, J I Nickerson, D A Medina, M W |
author_sort | Theusch, E |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5008997 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-50089972017-05-23 Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner Theusch, E Kim, K Stevens, K Smith, J D Chen, Y -D I Rotter, J I Nickerson, D A Medina, M W Pharmacogenomics J Original Article 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. Nature Publishing Group 2017-06 2016-03-01 /pmc/articles/PMC5008997/ /pubmed/26927283 http://dx.doi.org/10.1038/tpj.2016.12 Text en Copyright © 2017 Macmillan Publishers Limited http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/ |
spellingShingle | Original Article Theusch, E Kim, K Stevens, K Smith, J D Chen, Y -D I Rotter, J I Nickerson, D A Medina, M W Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner |
title | Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner |
title_full | Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner |
title_fullStr | Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner |
title_full_unstemmed | Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner |
title_short | Statin-induced expression change of INSIG1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner |
title_sort | statin-induced expression change of insig1 in lymphoblastoid cell lines correlates with plasma triglyceride statin response in a sex-specific manner |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5008997/ https://www.ncbi.nlm.nih.gov/pubmed/26927283 http://dx.doi.org/10.1038/tpj.2016.12 |
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