LEP G2548A和LEPR Q23R多态性与他汀类诱导的CK水平升高及代谢风险之间的相关性研究.docx

Abstract Hyperlipidemia，a common metabolic disease，is one of the most important risk factors of the cardiovascular and cerebrovascular diseases．And it is closely related to atherosclerosis，kidney disease，diabetes，obesity,fatty liver,especially associated with hypertension and cardio·cerebro vascular disease，which cause serious harm to people。S health．Statins are the most widely used lipid·lowering drugs in clinical practice．However,because of individual differences induced by genetic and environmental factors，the lipid—lowering effect of statins among individuals also exhibited considerable variation．Meanwhile,statins have certain side effects． Objectives：(1)To investigate whether LEP G2548A and LEPR Q223R polymorphisms influence serum lipid levels and whether the two polymorphisms affect the efficacy of simvastatin treatment in Chinese patients with primary hyperlipidemia．(2)To investigate the association of LEP G2548A and LEPR Q223R polymorphisms with statin—induced CK elevation and metabolic risks，such as hyperlipidemia，obesity and hype唱lycemia among Chinese patients with hyperlipidemia． Methods：Totally 734 patients with primary hyperlipidemia were recruited for the study from Beijing and Anhui，China．In this study,(1)We used an extreme。sampling approach by selecting 212 individuals from the top and bottom 15％of adjusted lipid-lowering response residuals to simvastatin(n=106 in each group of good or bad response)frOm a total of 734 samples with primary hyperlipidemia．(2)We enrolled 587 individuals from a total of 734 samples with hyperlipidemia．They were treated with simvastatin orally 20 mg／d．Fasting serum lipids，fasting glucose，creatine kinase and other parameters were measured at baseline and after 4 and 8 weeks of simvastatin treatment．Genotyping of LEP G2548A and LEPR Q223R was carried out using polymerase chain reaction·restriction fragment length polymorphism (PCR—RFLP)． Results：(1)More patients in the good response group(27％)had LEPR O．223R than in