Combinations of multiple genetic single nucleotide polymorphism sites related to individualized medication of statins and application thereof

Abstract

The invention provides combinations of multiple genetic single nucleotide polymorphism sites related to individualized medication of statins and application thereof. The combinations specifically comprise combinations of multiple genetic single nucleotide polymorphism sites respectively related to individual risks of coronary heart diseases, individual sensitivity to pharmacological action of statins on lowering of cholesterol (LDL-C) and individual susceptibility to adverse reaction of statins. The invention also provides a detection method directed at the combinations of the single nucleotide polymorphism sites and application of the combinations to construction of three-dimensional detection apparatuses and assessment and treatment apparatuses used for predicating and assessing individual risks of coronary heart diseases and statin intervention earnings, sensitivity to pharmacological action and dosage adjustment, and susceptibility to adverse reaction and management and control.

Description

technical field [0001] The invention relates to a combination of multiple gene single nucleotide polymorphism sites related to the individualized medication of statins and its application, specifically including the risk of coronary heart disease, the statins lowering cholesterol (LDL- C) combination of multiple gene single nucleotide polymorphism sites associated with three aspects of pharmacological action sensitivity and susceptibility to adverse reactions of statins and their application; the present invention also relates to the single nucleotide polymorphism for said single nucleotide Detection method of acid polymorphism site combination and its preparation for predicting and evaluating individual risk of coronary heart disease and benefit of statin drug intervention, pharmacological sensitivity and dose adjustment, susceptibility to adverse reactions and management control "three-dimensional" ” application in detection devices and evaluation processing devices Backgr...

AI Technical Summary

Problems solved by technology

In recent years, researchers at home and abroad have developed various detection methods and prediction and evaluation models based on the results of the above-mentioned genomics research. To establish a detection device and evaluation model that can predict the risk of coronary heart disease, but this device and model have no effect on the benefits of statin drug intervention, the sensitivity of the pharmacological effect of lowering LDL-C, and the susceptibility to adverse reactions. Genetic factors are detected and evaluated, so it is impossible to guide the individualized drug use of statins [see Chinese patent: Gu Dongfeng et al., "Single Nucleotide Polymorphism Site Combination of Multiple Genes Related to Coronary Heart Disease and Its Application" CN102762954B (2012 )]; Shiffman et al. from Celera Corporation of the United States identified loci associated with the risk of coronary heart disease and stroke from large-scale genomics studies, and these loci are also associated with statin drug intervention to reduce the risk of cardiovascular and cerebrovascular diseases Response is associated, but this technology does not specifically involve gene loci associated with statin pharmacological effects (LDL-C lowering effect) sensitivity or adverse reaction susceptibility, and it is impossible to fine-tune drug dosage or adverse reaction management and control, and cannot Realize individualized drug use of statin [see US patent: Shiffman et al. "Genetic polymorphisms associated with cardiovascular disease, methods of detection and uses thereof" US8216786B2 (2008); or US patent application "Genetic polymorphisms associated with statin response and cardiovascular disease methods of detection and uses thereof”US 20140235605 A1(2010)]; Schaefer et al. in the United States focused on the dose adjustment of statins, focusing on the role of the gene loci SLCO1B1 and ApoE in the pharmacological effects of statins, that is, the reduction of LDL-C response, but There is no systematic detection and evaluation of the genetic factors of individual coronary heart disease risk and intervention benefits [see US patent: Schaefer et al., "Composition and methods for treating and preventing coronary heart disease" US 8765377 (2011)]; while British Link et al. Just studied the relationship between the SLCO1B1 gene polymorphism and the risk of statin-induced skeletal myolysis [see Chinese patent application Link et al., "Diagnostic methods" CN 102016073 A(2008)]

[0011] In short, the various technologies currently emerging fail to integrate the individual's risk of coronary heart disease and the benefits of statin drug intervention, the sensitivity of pharmacological effects (lowering LDL-C), and the susceptibility to adverse reactions and other genetic factors and research results. Comprehensive analysis and induction failed to draw a panorama of the single nucleotide sites of genes significantly associated with the risk of coronary heart disease, the benefits of statin intervention, the sensitivity of pharmacological effects, and the susceptibility to adverse reactions in the individual genome, and it was impossible to provide comprehensive guidance Personalized statin medication; the lack of this technology also leads to a very low accuracy rate of statin drugs in clinical practice. The latest analysis shows that the accuracy rate of statin medication in the United States is only 5% [see literature Schork, "Personalized medicine: Time for one- person trial”Nature 520:609-611], which not only causes a huge waste of resources, but also may bring new risks such as statin-induced skeletal muscle lysis or new-onset type 2 diabetes to patients

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