br Acknowledgement This research was supported by a
Acknowledgement This research was supported by a grant from the National Research Foundation of Korea (NRF-2013R1A1A2011238) funded to Young-Mi Lee.
Introduction Stroke is considered a serious disease with high morbidity and high mortality. More than 6 million deaths are reported each year worldwide, and the majority of the deaths are reported from developing countries such as India and China. In the Chinese population, the incidence of stroke is estimated to be >2 million people. There are huge economic and social burdens because of stroke in China. Ischemic stroke (IS) is the most common type of stroke in China. According to epidemiologic studies, the incidence of IS in China is significantly higher than in developed countries. Stroke is a multifactorial disease influenced by both genetic and environmental factors. There were >160 causes associated with stroke; inflammation, atherosclerosis, and hyperlipidemia are the most common causes. It has been reported that lowering the level of LDL can retard atherosclerosis while reducing the incidence and mortality of IS.5, 6 It is well known that atorvastatin is a statin used worldwide with safety and tolerance. It is used to reduce blood lipid levels.7, 8, 9 However, some patients have a very poor response to atorvastatin therapy. There is evidence that genetic factors contribute to the response to atorvastatin therapy.11, 12 The goal of the present study was to describe the association between the candidate single nucleotide polymorphisms (SNPs) and the efficacy of atorvastatin. Cytochrome P450 (CYP450) is a group of structurally and functionally related superfamily tamoxifen citrate synthesis widely found in organisms. It plays an important role in the metabolism of substances, including endogenous (eg, fatty acids, steroids, prostaglandins, bile acids) and exogenous (eg, drugs, environmental carcinogens, food additives) substances. The human CYP450 gene has been basically defined, including 57 active genes and 58 pseudogenes. It was divided into 18 families and 44 subfamilies. In addition, there is a large number of alleles in these genes. Among the genes, CYP2C19, CYP2D6, and CYP3A4 are important subtypes of CYP450 genes involved in drug metabolism, which mediate 70% to 80% of the clinical drug metabolism in phase I metabolism and participate in exogenous chemical and endogenous substance metabolism. In the present study, 4 genes (CYP2C19, CYP2D6, CYP3A4, and CYP4F2) related to blood lipid or drug metabolism from the CYP450 superfamily genes were selected. Six SNPs in 4 genes were enrolled by using the minor allele frequency >0.05 as the standard, including rs4244285 and rs4986893 in the gene CYP2C19; rs3892097 and rs1065852 in the gene CYP2D6; rs2242480 in the gene CYP3A4; and rs2108622 in the gene CYP4F2. They have been shown to be related to drug metabolism or blood lipid levels. However, it is unclear whether SNPs influence the therapeutic effect of atorvastatin in patients with IS. We aimed to provide the correlation between the polymorphisms present in those genes and the therapeutic effect of atorvastatin on IS in the Chinese Han population.
Patients and Methods
Discussion Atherosclerosis is one of the most common risk factors for IS. The process of atherosclerosis is closely related to lipid metabolism. According to guidelines from the American Heart Association/American Stroke Association, lipid-lowering therapy is a common and effective means of treating IS. It has been reported that high levels of blood lipids promote the development of atherosclerosis. Reducing LDL-C levels could effectively attenuate the process of atherosclerosis. Atorvastatin is a statin used worldwide with better safety and tolerance. It was found that atorvastatin could significantly reduce the mortality and morbidity of IS.23, 24 However, some patients have a very poor response to therapy with this drug. These results indicate that genetic polymorphisms might affect drug efficacy.