**Pharmacogenomics**

**Chapter 7**

**Provisional chapter**

**Pharmacogenetics of Cardiovascular Disease: Genetic**

**Pharmacogenetics of Cardiovascular Disease: Genetic** 

Statins are very effective for lowering low-density lipoprotein cholesterol for primary and secondary cardiovascular disease prevention. While statins are usually well tolerated, individual response to statin therapy varies and intolerance, predominantly muscle symptoms, may appear in a significant proportion of patients. Besides clinical factors, variation in genes coding for proteins with drug transporting, immune or enzymatic function have been implicated in the pathogenesis of statin intolerance. In this review, we will characterise the candidate gene variants for development of statin intolerance, describe their population distribution and summarise current knowledge on their biological plausibility. Clinical relevance and current guidelines/recommendations will be

**Keywords:** genetic variation, pharmacogenetics, *SLCO1B1*, statin, statin-induced

Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase) inhibitors are highly effective drugs lowering plasmatic concentration of LDL-C cholesterol by 30–50% [1]. Despite the fact that they are usually considered safe and very well tolerated, a significant proportion of the treated patients does not tolerate the drug: they suffer from side effects, which may result in non-compliance of patients, drug dose-lowering and even discontinuation of therapy [2–4]. Undesirable effects of statins restrict their administration or reaching LDL-C cholesterol target values and limits effective treatment of patients at risk. Non-adherence or discontinuation

of therapy is associated with an increased risk of cardiovascular events [5–7].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

DOI: 10.5772/intechopen.79518

**Variation and Statin Intolerance**

**Variation and Statin Intolerance**

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.79518

**Abstract**

also discussed.

myopathy

**1. Introduction**

Jana Petrkova, Milos Taborsky and Martin Petrek

Jana Petrkova, Milos Taborsky and Martin Petrek

#### **Pharmacogenetics of Cardiovascular Disease: Genetic Variation and Statin Intolerance Pharmacogenetics of Cardiovascular Disease: Genetic Variation and Statin Intolerance**

DOI: 10.5772/intechopen.79518

Jana Petrkova, Milos Taborsky and Martin Petrek Jana Petrkova, Milos Taborsky and Martin Petrek

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.79518

#### **Abstract**

Statins are very effective for lowering low-density lipoprotein cholesterol for primary and secondary cardiovascular disease prevention. While statins are usually well tolerated, individual response to statin therapy varies and intolerance, predominantly muscle symptoms, may appear in a significant proportion of patients. Besides clinical factors, variation in genes coding for proteins with drug transporting, immune or enzymatic function have been implicated in the pathogenesis of statin intolerance. In this review, we will characterise the candidate gene variants for development of statin intolerance, describe their population distribution and summarise current knowledge on their biological plausibility. Clinical relevance and current guidelines/recommendations will be also discussed.

**Keywords:** genetic variation, pharmacogenetics, *SLCO1B1*, statin, statin-induced myopathy
