KR20160131227A

KR20160131227A - Method for providing the information for long-term prognosis in high-risk cardiovascular patients

Info

Publication number: KR20160131227A
Application number: KR1020150063105A
Authority: KR
Inventors: 이상학; 지선하; 박성하; 이지영
Original assignee: (주) 메디젠휴먼케어
Priority date: 2015-05-06
Filing date: 2015-05-06
Publication date: 2016-11-16
Also published as: KR101713535B1

Abstract

The present invention relates to a method for providing information on long-term prognosis for high-risk patients who are susceptible to cardiovascular diseases. More specifically, the present invention relates to a method for predicting a long-term risk that major cardiovascular diseases will occur in high-risk patients who are susceptible to cardiovascular diseases; and to a kit used to predict the prognosis of cardiovascular diseases. According to the present invention, the method for providing information comprises: a step of identifying the genotype of a single nucleotide polymorphism (rs9508025) in high-risk patients who are susceptible to cardiovascular diseases. Accordingly, the incidence of major cardiovascular events is predicted in early stages so the rate of death caused by major cardiovascular events can be greatly reduced.

Description

Methods for providing information on the long-term prognosis of high-risk cardiovascular disease patients.

The present invention relates to a method for providing information on a long-term prognosis of a high-risk group of cardiovascular diseases, and a kit for predicting the risk of major cardiovascular diseases in a high-risk group of patients with cardiovascular diseases and a kit for predicting prognosis.

Cardiovascular disease is a comprehensive term that includes all diseases that occur in the heart and major arteries, and refers to diseases such as heart disease or major arteries that are blocked, stretched or bleed. Major diseases of cardiovascular diseases include hypertension, ischemic heart disease, coronary artery disease, angina pectoris, myocardial infarction, atherosclerosis (atherosclerosis), cerebrovascular disease, stroke, arrhythmia. According to the 2009 statistics released by the National Statistical Office, cardiovascular diseases, including hypertensive diseases, ischemic heart diseases and cerebrovascular diseases, rank second only to malignant tumors, the second leading cause of death in Korea. It is known that mortality from cardiovascular diseases increases sharply in men over 55 years old and women over 65 years. One of the reasons for the high mortality associated with cardiovascular disease is that the number of patients with cardiovascular disease is continuously increasing due to the difficulty of early diagnosis because of the absence of special symptoms in cardiovascular diseases and the western eating habits, Because. Therefore, if the long-term prognosis of high-risk patients with cardiovascular disease can be predicted early, it is expected that mortality due to major cardiovascular events (MACE) can be significantly lowered through treatment and diet control.

Recently, it has been shown that genetic factors affect such cardiovascular diseases, and development of a method for predicting cardiovascular diseases using single nucleotide polymorphism (SNP) has been actively conducted worldwide (International Journal of Hypertension (2010) 281692: 13). However, the long-term prognosis of high-risk patients with cardiovascular disease has not been studied yet.

Therefore, there is an urgent need to develop a method for predicting the long-term prognosis of high-risk cardiovascular disease, that is, the risk of major cardiovascular events.

Disclosure of Invention Technical Problem [8] Accordingly, the present invention has been made in view of the above problems, and it is an object of the present invention to provide a method for predicting long-term prognosis of a high risk group of cardiovascular diseases using genotype analysis of single nucleotide polymorphism rs9508025.

However, the technical problem to be solved by the present invention is not limited to the above-mentioned problems, and other matters not mentioned can be clearly understood by those skilled in the art from the following description.

Hereinafter, various embodiments described herein will be described with reference to the drawings. In the following description, for purposes of complete understanding of the present invention, various specific details are set forth, such as specific forms, compositions, and processes, and the like. However, certain embodiments may be practiced without one or more of these specific details, or with other known methods and forms. In other instances, well-known processes and techniques of manufacture are not described in any detail, in order not to unnecessarily obscure the present invention. Reference throughout this specification to "one embodiment" or "embodiment" means that a particular feature, form, composition, or characteristic described in connection with the embodiment is included in at least one embodiment of the invention. Accordingly, the appearances of the phrase " in one embodiment "or" an embodiment "in various places throughout this specification are not necessarily indicative of the same embodiment of the present invention. In addition, a particular feature, form, composition, or characteristic may be combined in any suitable manner in one or more embodiments.

As used herein, the term "biological sample" refers to all samples for which gene information of a patient can be confirmed. Preferably, the sample is blood, plasma, serum, and the like, but is not limited thereto as long as it can identify single nucleotide polymorphisms.

As used herein, the term " method for providing information on the prognosis of cardiovascular diseases "is a method for providing information on the prediction of a risk of major cardiovascular events in a high-risk group of cardiovascular diseases in the long term, May include coronary heart disease death, non-fatal myocardial infarction, ischemic stroke, and unstable angina, but is not limited to cardiovascular related diseases.

As used herein, the term "kit" refers to a device for examining a single nucleotide polymorphism associated with the long-term prognosis of a high risk group of cardiovascular disease in Korea and providing information about the risk of major cardiovascular events , And there is no limitation as long as the polymorphism can be confirmed from the biological sample. Preferably a set of probes or primers having a sequence complementary to the single nucleotide polymorphic gene, wherein the "probe or primer" is an oligonucleotide having a sequence complementary to a single nucleotide polymorphism oliogonucleotide), and it is not limited as long as it can identify the genotype of the single nucleotide polymorphism rs9508025 of the present invention.

The present invention provides a method for providing information on the long-term prognosis of a high risk group of cardiovascular diseases, including identifying a genotype of rs9508025, a single nucleotide polymorphism (SNP) from a biological sample.

In one embodiment of the present invention, the method for providing the information is characterized by predicting that the genotype of rs9508025 is high risk group of major cardiovascular events (MACE) when CC is genotyped. In another embodiment of the present invention, the major cardiovascular event may be, but is not limited to, coronary heart disease death, non-fatal myocardial infarction, ischemic stroke, unstable angina, etc., but not limited to cardiovascular related diseases.

In yet another embodiment of the present invention, the method for providing the information is preferably for a Korean person. However, if the genotype of rs9508025 is analyzed, the long-term prognosis of high-risk cardiovascular disease can be predicted.

In another embodiment of the present invention, the biological sample is preferably not limited to blood, plasma or serum, as long as it can identify genetic information.

The invention also provides a kit for predicting long-term prognosis of a high risk group of cardiovascular diseases, comprising a complementary complementary probe or primer set for a single base polymorphism rs9508025.

The method of providing the information on the long-term prognosis of the cardiovascular disease high risk group according to the present invention is to identify the genotype of the single nucleotide polymorphism rs9508025 of the high risk group of cardiovascular diseases and to predict the incidence of major cardiovascular events early, Of the total population.

1 is a diagram illustrating Kaplan-Meier survival curves according to an embodiment of the present invention.

Hereinafter, the present invention will be described in more detail with reference to Examples. It will be apparent to those skilled in the art that these embodiments are only for describing the present invention in more detail and that the scope of the present invention is not limited by these embodiments in accordance with the gist of the present invention .

Example

Example 1: Identification of long-term prognostic-associated single nucleotide polymorphisms in high-risk cardiovascular disease

It is known to have a high association with coronary artery disease in order to identify single nucleotide polymorphism (SNP) in Koreans for predicting long-term prognosis of cardiovascular disease Single nucleotide polymorphisms rs1333049 and rs9508025 were selected and tested. rs1333049 is a single nucleotide polymorphism located on chromosome 9p21 and rs9508025 is a single nucleotide polymorphism located on the FLT1 (fms-related tyrosine kinase 1) gene. In order to confirm the association between the selected single nucleotide polymorphism and the long-term prognosis of cardiovascular disease, 2,814 subjects in the high-risk group of cardiovascular disease with hypertension or coronary artery disease among Koreans were selected and DNeasy blood & Genomic DNA was extracted by Tissue Kit (Qiagen) according to protocol, and genotypes of single base polymorphisms rs1333049 and rs9508025 were analyzed using Taqman SNP genotyping. The basic information of the experimental group used in this experiment is shown in Table 1. CAD in Table 1 means coronary artery disease. We then tracked the occurrence of major cardiovascular events (MACE) in the experimental group for an average of 8.8 years, followed by multivariate Cox proportional hazards model (multivariate risk model) to identify the association of major cardiovascular events with each single nucleotide polymorphism Cox-proportional hazard model) and expressed as Kaplan meier curve. Major cardiovascular events included coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, and unstable angina. The results are shown in Table 2 and Fig. HR in Table 2 represents the hazard ratio, and smokers included those who had smoked in the past.

[Table 1]

[Table 2]

During the follow-up period, major cardiovascular events occurred in 408 patients (14.5%) in the experimental group. Analysis of the single nucleotide polymorphism rs9508025 genotype of individuals with major cardiovascular events revealed that 27.6% of those with genotype CG and 48.9 And 23.2% for those with genotype GG, and the hazard ratio for genotype CC was 1.21. The results showed that the CC genotype of the single nucleotide polymorphism rs9508025 was highly correlated with the occurrence of major cardiovascular events.

On the other hand, the single nucleotide polymorphism rs1333049 was not associated with major cardiovascular events.

These results indicate that the single nucleotide polymorphism rs1333049 has a high correlation with coronary artery disease but does not correlate with the occurrence of major cardiovascular events in the long term. It was confirmed that single nucleotide polymorphism did not correlate with the occurrence of major cardiovascular events in the long term. In addition, we confirmed that the single nucleotide polymorphism rs9508025 has a high correlation with long-term major cardiovascular events when the genotype is CC. Through the genotype analysis of the single nucleotide polymorphism rs9508025, Can be predicted.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the same is by way of illustration and example only and is not to be construed as limiting the scope of the present invention. It is therefore intended that the scope of the invention be defined by the claims appended hereto and their equivalents.

Claims

Identifying a genotype of rs9508025, a single nucleotide polymorphism (SNP) from a biological sample. &Lt; RTI ID = 0.0 > 8. < / RTI >

The method according to claim 1,
Wherein the method for providing the information provides information on the prognosis of the high risk group of cardiovascular disease.

The method according to claim 1,
The method of providing the information is characterized by predicting that the genotype of rs9508025 is a high risk group of major cardiovascular events (MACE) when CC is a method of providing information on cardiovascular disease prognosis.

The method of claim 3,
Wherein the major cardiovascular event is at least one selected from the group consisting of coronary heart disease death, non-fatal myocardial infarction, ischemic stroke, and unstable angina pectoris.

The method according to claim 1,
A method for providing information on cardiovascular disease prognosis, the method comprising providing the information to a Korean patient.

The method according to claim 1,
Wherein said biological sample is blood, plasma, or serum.

A kit for predicting cardiovascular disease prognosis, comprising a complementary complementary probe or primer set for a single nucleotide polymorphism rs9508025.

8. The method of claim 7,
Wherein said kit provides information on the long-term prognosis of a high-risk group of cardiovascular diseases.

8. The method of claim 7,
Wherein said kit predicts that the genotype of rs9508025 is high risk group of major cardiovascular events (MACE) when CC is genotype.

10. The method of claim 9,
Wherein the major cardiovascular event is at least one selected from the group consisting of coronary heart disease death, non-fatal myocardial infarction, ischemic stroke, and unstable angina pectoris.