Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2011 Feb;89(2):210-6.
doi: 10.1038/clpt.2010.255. Epub 2010 Dec 22.

Common nonsynonymous substitutions in SLCO1B1 predispose to statin intolerance in routinely treated individuals with type 2 diabetes: a go-DARTS study

L A Donnelly  1 , A S F Doney, R Tavendale, C C Lang, E R Pearson, H M Colhoun, M I McCarthy, A T Hattersley, A D Morris, C N A Palmer
Affiliations

Common nonsynonymous substitutions in SLCO1B1 predispose to statin intolerance in routinely treated individuals with type 2 diabetes: a go-DARTS study

L A Donnelly et al. Clin Pharmacol Ther. 2011 Feb.

Abstract

SLCO1B1 gene variants are associated with severe statin-induced myopathy. We examined whether these variants are also associated with general statin intolerance in a large population of patients with type 2 diabetes receiving statins as part of routine clinical care. A total of 4,196 individuals were genotyped for rs4149056 (Val174Ala) and rs2306283 (Asp130Asn). Intolerance was defined by serum biochemistry and also by discontinuation, switching, or reduction in dose of the prescribed statin drug. Ala174 was associated with higher intolerance (odds ratio = 2.05, P = 0.043), whereas Asp130 was associated with lower intolerance (odds ratio = 0.71, P = 0.026). Ala174 was associated with a lower low-density lipoprotein cholesterol (LDLc) response to statins (P = 0.01) whereas 130D was associated with a greater LDLc response to statins (P = 0.048), as previously reported; however, this association was no longer present when data for statin-intolerant individuals were removed from the analysis. This study suggests that common genetic variants selected for an extreme phenotype of statin-induced myopathy also predispose to more common milder statin intolerance and may, for this reason, impact lipid-lowering efficacy.

PubMed Disclaimer

Figures

Figure 1
Figure 1. Frequency of intolerance in whole population stratified by dose
In order to contextualize the putative risk burden for intolerance in the entire statin treated population conferred by this variation, we coded the individuals who we could positively identify as intolerant as 1, and coded all other statin treated individuals as 0 regardless of the classification for tolerance. The data was then stratified by dose group as those treated with less than 40mg statin (simvastatin equivalent, Low Dose) and those treated with 40mg statin or above (simvastatin equivalent, High Dose). P values shown are for Chi squared tests for trend (1df.) across the SLCO1B1 genotype score.
See this image and copyright information in PMC

Comment in

References

    1. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366:1267–78. - PubMed
    1. Armitage J. The safety of statins in clinical practice. Lancet. 2007;370:1781–90. - PubMed
    1. Lansberg PJ, Mitchel YB, Shapiro D, Kastelein JJ, Altman R, Jerums G, et al. Long-term efficacy and tolerability of simvastatin in a large cohort of elderly hypercholesterolemic patients. Atherosclerosis. 1995;116:153–62. - PubMed
    1. Simons LA, Levis G, Simons J. Apparent discontinuation rates in patients prescribed lipid-lowering drugs. Med J Aust. 1996;164:208–11. - PubMed
    1. Pedan A, Varasteh L, Schneeweiss S. Analysis of factors associated with statin adherence in a hierarchical model considering physician, pharmacy, patient, and prescription characteristics. J Manag Care Pharm. 2007;13:487–96. - PMC - PubMed

Publication types

Substances