Abstract
We investigated the associations of LEP G2548A and LEPR Q223R polymorphisms with statin-induced creatine kinase (CK) elevation among Chinese patients with hyperlipidemia. A total of587 enrolled individuals were treated with 20 mg/d oral simvastatin for 8 consecutive weeks. Genotyping of LEP G2548A and LEPR Q223R were conducted using PCR-RFLP. Multiple regression analyses showed that, in the Dongzhi region only, patients carrying the LEP AA genotype had a significantly greater increase in CK levels compared to those carrying the AG+GG genotypes after four weeks (P = 0.004) and eight weeks (P < 0.001) consecutive simvastatin treatment. Patients were further divided into three groups based on the tertiles of the CK distribution. Compared to subjects in the lowest tertile of CK elevation, the adjusted relative odds of having the AG+GG genotypes among subjects in the highest tertile was 0.5 (95% CI, 0.3 to 0.7) and 0.4 (95% CI, 0.2 to 0.6) after the fourth and eighth weeks, respectively. The interaction terms between the Beijing or Dongzhi region and the LEP GA+AA genotypes were marginally significant for CK elevation at the fourth week (P = 0.057) and significant for CK elevation at the eighth week (P = 0.002). The adverse effect of the LEP G2548A polymorphism on increasing CK levels may be dependent on the environmental milieu. It suggests that lifestyle interventions might offset the side effects of simvastatin therapy among those with genetic susceptibility. Further research is needed to identify specific individual-level factors for clinical practice that modify the effect of genotype.
Highlights
3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase inhibitors, commonly known as statins, are believed to inhibit cholesterol biosynthesis and are the most widely used cholesterol-lowering drugs to treat hypercholesterolemia [1, 2]
We investigated the associations of LEP G2548A and LEPR Q223R polymorphisms with statin-induced creatine kinase (CK) elevation among Chinese patients with hyperlipidemia
body mass index (BMI), waist circumference (WC), systolic blood pressure (SBP), fasting glucose, HDL, low-density lipoprotein (LDL), and CK, significant differences were observed between the Beijing and Dongzhi cohorts
Summary
3-hydroxy-3-methylglutaryl-coenzyme A (HMGCoA) reductase inhibitors, commonly known as statins, are believed to inhibit cholesterol biosynthesis and are the most widely used cholesterol-lowering drugs to treat hypercholesterolemia [1, 2]. Statins disturb cholesterol biosynthesis by hindering the activity of HMG-CoA reductase in the rate-limiting step of cholesterol synthesis This inhibition leads to increased levels of low-density lipoprotein (LDL) receptors, which results in increased uptake and degradation of low-density lipoprotein www.impactjournals.com/oncotarget cholesterol (LDL-C), reduced cholesterol accumulation, and decreased lipoprotein secretion and cholesterol synthesis. CK catalyzes the conversion of creatine (Cr) and creates phosphocreatine (PCr) and adenosine diphosphate (ADP) using adenosine triphosphate (ATP) This is an important mechanism in the cellular energy supply chain for safeguarding in tissues with inconstant energy demands, namely skeletal and cardiac muscle [10]. The common G2548A polymorphism of the LEP gene has been tied to serum leptin and BMI in obese individuals [17, 18]. Khera et al analyzed data for participants in three prospective cohorts and one cross-sectional study to find that both genetic and lifestyle factors contribute to individual-level risk of coronary artery disease, but increased genetic risk can be offset largely by a healthy lifestyle [23]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
