Statin-induced LDL cholesterol response and type 2 diabetes: a bidirectional two-sample Mendelian randomization study.,The Pharmacogenomics Journal

当前位置： X-MOL 学术 › Pharmacogenomics J. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Statin-induced LDL cholesterol response and type 2 diabetes: a bidirectional two-sample Mendelian randomization study.
The Pharmacogenomics Journal ( IF 2.9 ) Pub Date : 2019-12-05 , DOI: 10.1038/s41397-019-0125-x
Roelof A J Smit _{1,

2} , Stella Trompet _{1,

2} , Aaron Leong _{3,

4} , Mark O Goodarzi _{5,

6} , Iris Postmus ₂ , Helen Warren _{7,

8} , Elizabeth Theusch ₉ , Michael R Barnes _{7,

8} , Benoit J Arsenault _{10,

11} , Xiaohui Li ₁₂ , QiPing Feng _{13,

14} , Daniel I Chasman _{4,

15} , L Adrienne Cupples _{16,

17} , Graham A Hitman ₁₈ , Ronald M Krauss ₉ , Bruce M Psaty _{19,

20} , Jerome I Rotter _{12,

21} , Saskia le Cessie _{22,

23} , C Michael Stein _{13,

14} , J Wouter Jukema _{1,

24} ,

Affiliation

Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands.
Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
Division of General Internal Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA.
Harvard Medical School, Boston, MA, 02115, USA.
Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
William Harvey Research Institute, Barts and The London School of Medicine, Queen Mary University of London, London, EC1M 6BQ, UK.
National Institute for Health Research, Barts Cardiovascular Biomedical Research Center, Barts and The London School of Medicine, Queen Mary University of London, London, EC1M 6BQ, UK.
Children's Hospital Oakland Research Institute, 5700 Martin Luther King Jr Way, Oakland, CA, 94609, USA.
Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, QC, Canada.
Department of Medicine, Faculty of Medicine, Université Laval, Québec, QC, Canada.
The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Department of Medicine, Vanderbilt University, Nashville, TN, USA.
Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.
Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, 02215, USA.
Department of Biostatistics, Boston University School of Public Health, Boston, MA, 02118, USA.
NHLBI Framingham Heart Study, Framingham, MA, 01702, USA.
Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology and Health Services, University of Washington, Seattle, WA, 98101, USA.
Kaiser Permanente Washington Health Research Institute, Seattle, WA, 98101, USA.
The Institute for Translational Genomics and Population Sciences, Department of Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Section of Medical Statistics, Department of Biomedical Data Sciences, Leiden University Medical Center, Leiden, The Netherlands.
Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, The Netherlands.

It remains unclear whether the increased risk of new-onset type 2 diabetes (T2D) seen in statin users is due to low LDL-C concentrations, or due to the statin-induced proportional change in LDL-C. In addition, genetic instruments have not been proposed before to examine whether liability to T2D might cause greater proportional statin-induced LDL-C lowering. Using summary-level statistics from the Genomic Investigation of Statin Therapy (GIST, n_max = 40,914) and DIAGRAM (n_max = 159,208) consortia, we found a positive genetic correlation between LDL-C statin response and T2D using LD score regression (r_genetic = 0.36, s.e. = 0.13). However, mendelian randomization analyses did not provide support for statin response having a causal effect on T2D risk (OR 1.00 (95% CI: 0.97, 1.03) per 10% increase in statin response), nor that liability to T2D has a causal effect on statin-induced LDL-C response (0.20% increase in response (95% CI: −0.40, 0.80) per doubling of odds of liability to T2D). Although we found no evidence to suggest that proportional statin response influences T2D risk, a definitive assessment should be made in populations comprised exclusively of statin users, as the presence of nonstatin users in the DIAGRAM dataset may have substantially diluted our effect estimate.

中文翻译：

他汀类药物诱导的LDL胆固醇反应和2型糖尿病：双向两次孟德尔随机抽样研究。

他汀类药物使用者出现新发2型糖尿病（T2D）的风险增加是由于低LDL-C浓度还是由于他汀类药物引起的LDL-C比例变化所致。此外，之前尚未提出遗传仪器来检查对T2D的责任是否可能导致更大比例的他汀类药物引起的LDL-C降低。使用他汀类药物治疗基因组研究（GIST，n _max = 40,914）和DIAGRAM（n _max = 159,208）联盟的汇总水平统计数据，我们使用LD评分回归发现LDL-C他汀类药物应答与T2D之间存在正相关的遗传关系（r_遗传的 = 0.36，se = 0.13）。但是，孟德尔随机分析未提供对他汀类药物反应具有T2D风险因果关系的支持（每增加10％他汀类药物反应可导致OR 1.00（95％CI：0.97，1.03）或因果关系）对T2D风险也没有因果关系他汀类药物诱导的LDL-C应答（对T2D的责任几率翻倍，应答增加0.20％（95％CI：-0.40，0.80））。尽管我们没有发现证据表明比例他汀类药物反应会影响T2D风险，但应在仅由他汀类药物使用者组成的人群中进行最终评估，因为DIAGRAM数据集中存在非他汀类药物使用者可能会大大稀释我们的疗效估计值。

更新日期：2019-12-05

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文