WO2018043822A1 - Méthode de diagnostic et kit de diagnostic permettant un diagnostic de l'apparition, ou non, d'une dépression post-syndrome coronarien aigu à l'aide de l'interleukine 1β - Google Patents

Méthode de diagnostic et kit de diagnostic permettant un diagnostic de l'apparition, ou non, d'une dépression post-syndrome coronarien aigu à l'aide de l'interleukine 1β Download PDF

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WO2018043822A1
WO2018043822A1 PCT/KR2016/013327 KR2016013327W WO2018043822A1 WO 2018043822 A1 WO2018043822 A1 WO 2018043822A1 KR 2016013327 W KR2016013327 W KR 2016013327W WO 2018043822 A1 WO2018043822 A1 WO 2018043822A1
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depression
coronary syndrome
acute coronary
acute
concentration
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Korean (ko)
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김재민
강희주
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전남대학교산학협력단
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    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6893—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids related to diseases not provided for elsewhere
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/156—Polymorphic or mutational markers
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00—Oligonucleotides characterized by their use
    • C12Q2600/158—Expression markers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/52—Assays involving cytokines
    • G01N2333/54—Interleukins [IL]
    • G01N2333/545—IL-1

Definitions

  • the present invention relates to a method for diagnosing depression, and more specifically, a diagnostic method for predicting depression after acute coronary syndrome by analyzing the concentration and genotype of a specific biomarker in the blood of a patient with acute coronary syndrome.
  • diagnostic kits for diagnostic kits.
  • Depression is often accompanied by acute coronary syndrome (ACS).
  • ACS acute coronary syndrome
  • depression with ACS predicts a poor prognosis
  • Corresponding mechanisms for the link between depression and ACS were investigated, and the inflammatory hypothesis was highlighted. Inflammation is associated with serotonin disorders and hypothalamic-pituitary-adrenal axis hyperactivity, and the inflammatory process is involved in the pathophysiology of depression (Maes et al., 2011A, Lee et al., 2013).
  • the role of inflammation in the etiology and risk of onset of ACS is well documented, and the magnitude of the inflammatory response during ACS predicts the prognosis of heart disease (BERTON et al., 2009).
  • inflammation is not only associated with depression and ACS separately (Maes et al. 2011B) but also with poor prognosis of ACS (Poole et al., 2011).
  • previous studies have suggested a significant association between depression and inflammatory markers including C-reactive protein and cytokines in ACS (Wilkowska et al., 2015).
  • Interleukin (IL) -1 ⁇ an important proinflammatory cytokine that induces the production of other cytokines, is associated with poor prognosis of ACS by contributing to the development of atherosclerosis. It has been shown that depression / burnout patients in ACS have higher IL-1 ⁇ concentrations (Appels et al., 2000), and escitalopram has been shown to lower IL-1 ⁇ concentrations in ACS model mice (Bah et al., 2011). Recent in vitro studies have shown that IL-1 ⁇ signaling is involved in the inflammatory cascade in the development of depression in ACS patients, and that statins act as anti-inflammatory agents by down-regulating IL-1 ⁇ (Ma et al., 2016).
  • IL-1 ⁇ secretion is regulated by IL-1 ⁇ gene polymorphism: individuals with -511T or + 3953T secreted higher concentrations of IL-1 ⁇ than individuals with -511C or + 3953C polymorphisms.
  • the present inventors have completed the present invention by revealing that the IL-1 ⁇ blood concentration and gene polymorphism have a significant correlation with the onset of depression after acute coronary syndrome.
  • the objective of the present invention is to analyze the acute coronary syndrome in patients with acute coronary syndrome and acute coronary syndrome through the analysis of IL-1 ⁇ concentration and IL-1 ⁇ gene polymorphism. It is to provide a method for diagnosing depression after arterial syndrome.
  • Another object of the present invention is to measure the IL-1 ⁇ concentration and IL-1 ⁇ polymorphism in the blood of patients with acute coronary syndrome, so that the diagnosis of acute stage depression after acute coronary syndrome can be predicted and diagnosed. It is to provide a diagnostic kit for depression after acute coronary syndrome, which can prevent depression in advance.
  • the present invention comprises a measurement step of measuring the IL-1 ⁇ concentration in the blood of patients with acute coronary syndrome; Genotyping step of investigating IL-1 ⁇ -511C / T polymorphism of the patient; And a diagnosis step of determining whether acute depression is developed according to the measured IL-1 ⁇ concentration and the analyzed IL-1 ⁇ -511C / T genotype.
  • the first condition wherein the measured IL-1 ⁇ concentration is greater than or equal to the reference concentration in the diagnosis step and the second condition wherein the IL-1 ⁇ -511C / T genotype of the analyzed patient is ?? 511T / T genotype. It is judged that the acute depression is developed only when all are satisfied.
  • the incidence of acute depression is assessed to be 58% or greater when the first and second conditions are met.
  • a 56% chance of developing acute depression is not diagnosed if the first and second conditions are not met.
  • the baseline concentration is 3.5 pg per ml of serum.
  • the genotyping step comprises the steps of: separating the DNA comprising the 511th base of the IL-1 ⁇ gene isolated from the patient; Amplifying the separated DNA using a sense primer and an antisense primer; And examining the presence of IL-1 ⁇ -511TT genotype by examining the amplified DNA using a restriction enzyme capable of recognizing a 511C ⁇ T mutation.
  • the present invention provides a measurement means for measuring the serum IL-1 ⁇ concentration in the blood of the patient; And genotyping means for analyzing the IL-1 ⁇ -511C / T gene polymorphism of the patient and analyzing whether or not it possesses the -511TT genotype; and providing a diagnosis kit for acute coronary syndrome after depression.
  • the present invention has the following effects.
  • the presence of acute coronary syndrome predicts acute stage of depression in patients with acute coronary syndrome through analysis of IL-1 ⁇ concentration and IL-1 ⁇ gene polymorphism. Can be diagnosed.
  • the diagnostic kit for acute coronary syndrome syndrome is to determine the incidence of acute stage depression after acute coronary syndrome simply by measuring the IL-1 ⁇ concentration and IL-1 ⁇ gene polymorphism in the blood of patients with acute coronary syndrome. Because it can be predicted and diagnosed, it is possible to prevent the depression of the patient preemptively and has clinical usefulness.
  • IL-1 ⁇ interleukin-1 ⁇ due to two gene polymorphisms and depressive disorder states at baseline and follow-up after acute coronary syndrome (ACS).
  • first and second may be used to describe various components, but the components should not be limited by the terms. The terms are used only for the purpose of distinguishing one component from another.
  • the first component may be referred to as the second component, and similarly, the second component may also be referred to as the first component.
  • temporal after-degree relationship for example, if the temporal after-degree relationship is described as 'after', 'following', 'after', 'before', etc. This includes non-consecutive cases unless' is used.
  • each of the various embodiments of the present invention can be combined or combined with each other, partly or wholly, and technically various interlocking and driving are possible, and each of the embodiments can be implemented independently or in relation to each other. It can also be done together.
  • the technical features of the present invention reveal that IL-1 ⁇ blood concentration and IL-1 ⁇ -511C / T gene polymorphism are significantly associated with the development of depression after acute coronary syndrome.
  • the present invention provides a method and a diagnostic kit for diagnosing depression after acute coronary syndrome using a blood marker of IL-1 ⁇ and IL-1 ⁇ -511C / T polymorphism as a biomarker to predict and / or diagnose the disease. .
  • the method for diagnosing depression after acute coronary syndrome includes measuring a concentration of IL-1 ⁇ in the blood of a patient having acute coronary syndrome; Genotyping step of investigating IL-1 ⁇ -511C / T polymorphism of the patient; And a diagnosis step of determining whether acute depression is developed according to the measured IL-1 ⁇ concentration and the analyzed IL-1 ⁇ -511C / T genotype.
  • the reference concentration may be defined as a concentration of 3.5pg per 1ml serum
  • the acute phase means a period within two weeks from the time of the occurrence of acute coronary syndrome
  • acute depression is the point when the acute coronary syndrome occurs Depression occurs onset within two weeks.
  • genotyping may include separating the DNA comprising the 511 th base of the IL-1 ⁇ gene isolated from the patient; Amplifying the separated DNA using a sense primer and an antisense primer; And examining the presence of the IL-1 ⁇ -511TT genotype by examining the amplified DNA using a restriction enzyme capable of recognizing a 511C ⁇ T mutation.
  • the acute coronary syndrome syndrome depression kit of the present invention is a diagnostic means for measuring the serum IL-1 ⁇ concentration in the blood of the patient; And genotyping means for analyzing the patient's IL-1 ⁇ -511C / T gene polymorphism to analyze whether or not it possesses the -511TT genotype.
  • the present invention is one or more of IL-1 ⁇ concentration and IL-1 ⁇ -511C / T polymorphism of the patient after acute coronary syndrome affects the depression after acute coronary syndrome, in particular blood IL- above the reference concentration
  • We predicted the onset of acute depression associated with acute coronary syndrome by proving that the interaction between 1 ⁇ concentration and IL-1 ⁇ -511T / T genotype is significantly related to the development of acute depression after acute coronary syndrome. It has significant clinical advantages by providing diagnostic methods and diagnostic kits that can be used to treat depression that worsens the prognosis of acute coronary syndrome. That is, by using the present invention it is possible to facilitate the prevention and treatment by selecting a patient prone to depression associated with acute coronary syndrome with a large disease burden.
  • K-DEPACS Korean Depression
  • ACS acute coronary syndrome
  • Diagnosis of depressive disorders was performed using a structured DSM-IV mental and diagnostic interview defining MINI, a major or minor depressive disorder. Interviews have been translated into Korean and standardized (Yoo et al., 2006). Since ACS patients are usually discharged within two weeks of intensive care, they did not require a duration of symptoms longer than two weeks at baseline as a diagnostic criterion for depressive disorder. However, a standard two-week symptom duration was needed for follow-up diagnosis. Since there were not many patients with major depression that could be analyzed separately, patients with major and minor depression were included in the study in the same category. Baseline and one-year follow-up assessments were used to assess depression in the acute and chronic phases of ACS.
  • Serum IL-1 ⁇ concentrations were analyzed using a solid-phase sandwich enzyme immunoassay kit (Invitrogen, Camaro, CA, USA).
  • IL-1 ⁇ genotype was investigated using polymerase chain reaction (PCR) and PCR-based restriction fragment length polymorphism analysis, considering -511C / T or + 3953C / T. Taking into account the infrequency of the + 3953T / T genotype, they divided into two groups (C / C or C / T).
  • PCR polymerase chain reaction
  • DNA isolation was isolated from leukocytes extracted from the patient's blood using a DNA extraction kit (QIAmp blood kit, Qiagen) according to the manufacturer's protocol.
  • the isolated DNA samples were amplified with a GeneAmp PCR machine (Perkin Elmer 9600) using a primer set (sense primer (5'-TGAAGGAGAAGGTGTCTGCGGGA-3 ') and antisense primer (5'-AGGACGGTGCGGTGAGAGTG-3').
  • sense primer 5'-TGAAGGAGAAGGTGTCTGCGGGA-3 '
  • antisense primer 5'-AGGACGGTGCGGTGAGAGTG-3'.
  • the amplified fragments were digested at 37 ° C. for 4 hours with a restriction enzyme Hin f1 (10 unit / reaction mixture, purchased from MBI Fermentas) that can recognize 511C ⁇ T mutations in the amplified fragments.
  • Hin f1 10 unit / reaction mixture, purchased from MBI Fermentas
  • the fragments treated with Hin f1 were then electrophoresed with polyacrylamide gel and stained with EtBr (ethidium bromide) to observe the mutated state.
  • Baseline variables including demographic data, depression characteristics, cardiovascular risk factors, and current heart condition, were compared according to depression at baseline using the t-test or ⁇ 2 test. Then, features with significant relevance (P ⁇ 0.05) were considered as covariates in multivariate analysis.
  • IL-1 ⁇ concentration and two genotypes were compared using the t-test and the ⁇ 2 test. To determine the effect of potential interactions, the association between depression status and IL-1 ⁇ concentration was initially analyzed according to the two genotypes. The interaction between IL-1 ⁇ concentration and each genotype was then analyzed using a multivariate logistic regression model after appropriate covariate adjustments.
  • the sensitivity analysis was performed using the same statistical method except for participants with a history of depression. All analyzes were performed using SPSS 18.0.
  • Table 2 shows that ACS patients with acute depression, or depression at baseline, have significantly higher IL-1 ⁇ concentrations and more -511T alleles. In contrast, no association with the + 3953T / T genotype was found. At follow-up, depression was not related to IL-1 ⁇ concentration or genotype. All genotypes were at Hardy-Wineberg equilibrium (all P> 0.05).
  • serum IL-1 ⁇ concentration and IL-1 ⁇ -511C / T genotyping may be clinically useful because screening to identify groups at risk of depressive disorder in the acute phase of ACS is possible and appropriate therapeutic intervention is possible. Can be.
  • depression accompanied by ACS leads to very high disease burden and makes treatment difficult.
  • the present invention only by analyzing IL-1 ⁇ concentration and IL-1 ⁇ -511C / T genotype at baseline, May enable more focused interventions in the prevention and / or management of depression associated with ACS. This is because vulnerable patients with genetic predisposition at high IL-1 ⁇ levels are more likely to experience ACS-associated depression.
  • the usefulness of the present invention is that if a doctor is aware of the effects of IL-1 ⁇ concentration and -511C / T genotype on ACS post-ACS, it may be more focused on depression during ACS, leading to acute depression after ACS. Prevent or preemptively treat the disease early onset.

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Abstract

La présente invention concerne une méthode de diagnostic de l'apparition, ou non, d'une dépression et, plus particulièrement, une méthode de diagnostic et un kit de diagnostic permettant de prédire l'apparition, ou non, d'une dépression post-syndrome coronarien aigu par analyse de la concentration et du génotype d'un biomarqueur particulier dans le sang d'un patient souffrant d'un syndrome coronarien aigu.
PCT/KR2016/013327 2016-08-30 2016-11-18 Méthode de diagnostic et kit de diagnostic permettant un diagnostic de l'apparition, ou non, d'une dépression post-syndrome coronarien aigu à l'aide de l'interleukine 1β WO2018043822A1 (fr)

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KR1020160110894A KR101903505B1 (ko) 2016-08-30 2016-08-30 인터루킨 1β를 이용한 급성관상동맥증후군후 우울증발병여부 진단방법 및 진단키트

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KR102123021B1 (ko) 2018-07-26 2020-06-16 재단법인 대구경북과학기술원 세로토닌 재흡수 억제제 계열 항우울제에 대한 반응성 조절용 펩티드 및 이의 용도
KR102214214B1 (ko) * 2020-06-30 2021-02-08 가천대학교 산학협력단 청년기 우울증 질환을 진단하기 위한 조성물 및 키트

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US20070003981A1 (en) * 2005-06-29 2007-01-04 Rules-Based Medicine, Inc. Methods and kits for the diagnosis of acute coronary syndrome

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20070003981A1 (en) * 2005-06-29 2007-01-04 Rules-Based Medicine, Inc. Methods and kits for the diagnosis of acute coronary syndrome

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
KANG: "Comorbidity of Depression with Physical Disorders: Research and Clinical Implications", CHONNAM MEDICAL JOURNAL, vol. 51, 14 April 2015 (2015-04-14), pages 8 - 18, XP055605115 *
MIRANDA-MALPICA: "The interleukin IB-511 polymorphism is associated with the risk of developing restenosis after coronary stenting in Mexican patients", HUMAN IMMUNOLOGY, vol. 69, 2008, pages 116 - 121, XP022551761 *
POOLE, LYDIA ET AL.: "The puzzle of depression and acute coronary syndrome: Reviewing the role of acute inflammation", JOURNAL OF PSYCHOSOMATIC RESEARCH, vol. 71, no. 2, 2011, XP028240072, DOI: 10.1016/j.jpsychores.2010.12.009 *
SOYLU O: "Interleukin-1B (-511) gene polymorphism is associatedwith acute coronary syndrome in the Turkish population", EUROPEAN CYTOKINE NETWORK, vol. 19, 2008, pages 42 - 48, DOI: 10.1684/ecn.2008.0119 *

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