WO2025164902A1 - Marqueur de polymorphisme mononucléotidique associé à une réduction du score de copie de figure complexe de rey pour prédire le risque de développer la maladie d'alzheimer et son utilisation - Google Patents

Marqueur de polymorphisme mononucléotidique associé à une réduction du score de copie de figure complexe de rey pour prédire le risque de développer la maladie d'alzheimer et son utilisation

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Publication number
WO2025164902A1
WO2025164902A1 PCT/KR2024/018860 KR2024018860W WO2025164902A1 WO 2025164902 A1 WO2025164902 A1 WO 2025164902A1 KR 2024018860 W KR2024018860 W KR 2024018860W WO 2025164902 A1 WO2025164902 A1 WO 2025164902A1
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WIPO (PCT)
Prior art keywords
disease
risk
polynucleotide
developing alzheimer
predicting
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PCT/KR2024/018860
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English (en)
Korean (ko)
Inventor
원성호
이건호
박준영
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SNU R&DB Foundation
Chosun University Industry Academic Cooperation Foundation
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Seoul National University R&DB Foundation
Chosun University Industry Academic Cooperation Foundation
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Publication of WO2025164902A1 publication Critical patent/WO2025164902A1/fr
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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
    • 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
    • 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
    • C12Q1/6813—Hybridisation assays
    • C12Q1/6834—Enzymatic or biochemical coupling of nucleic acids to a solid phase
    • C12Q1/6837—Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips
    • 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

Definitions

  • the present invention relates to a method for predicting the risk of developing Alzheimer's disease by identifying a specific single nucleotide polymorphism (SNP) that has a significant correlation with the risk of developing Alzheimer's disease, a composition for predicting the risk of developing Alzheimer's disease comprising a polynucleotide, polypeptide, antibody or cDNA capable of identifying the SNP, and a microarray and kit comprising the same.
  • SNP single nucleotide polymorphism
  • Alzheimer's disease is a progressive disorder that causes cognitive impairment and memory loss.
  • Major risk factors for Alzheimer's disease include age, family history, and lifestyle.
  • Alzheimer's disease involves a chronic, progressive process leading to neurodegeneration, including axonal damage, cell death, and gliosis.
  • the pathogenesis and pathophysiology of neurodegenerative diseases are complex and only a small part of the underlying cause is understood.
  • a mutation at a frequency of about 1 per 1,000 bases which is called a single nucleotide polymorphism (SNP).
  • SNP single nucleotide polymorphism
  • a 5% polymorphism is called a common polymorphism
  • a 1 to 5% polymorphism is called a rare polymorphism.
  • GWAS genome-wide association study
  • GWAS genome-wide association study
  • RCFT Rey Complex Figure Test assesses visual memory/visual-spatial abilities. It can measure imitation time, imitation score, immediate recall, delayed recall, true positives, false positives, positive positives, recognition index, and nonspecific recognition errors.
  • the inventors of the present invention identified a variant of SNP that indicates the risk of developing Alzheimer's disease, confirmed that the decline in the Rayleigh complex shape test was greater in the presence of such a variant, and developed a method for providing information that can evaluate the possibility of developing Alzheimer's dementia in an individual, thereby completing the present invention.
  • the purpose of the present invention is to provide a method for predicting the risk of developing Alzheimer's disease by identifying specific SNPs that have a significant correlation with the risk of Alzheimer's disease in a genetic sample obtained from a patient.
  • Another object of the present invention is to provide a method for providing information for predicting the risk of developing Alzheimer's disease by identifying specific SNPs that have a significant correlation with the risk of Alzheimer's disease in a genetic sample obtained from a patient.
  • Another object of the present invention is to provide a microarray for predicting the risk of developing Alzheimer's disease, comprising a polynucleotide, a polypeptide, an antibody therefor, or a cDNA thereof capable of identifying a specific SNP marker.
  • Another object of the present invention is to provide a kit for predicting the risk of developing Alzheimer's disease, comprising a polynucleotide, polypeptide, antibody therefor, or cDNA thereof capable of identifying a specific SNP marker.
  • the inventors of the present invention have made extensive research efforts to develop a technology that can more effectively predict the onset of Alzheimer's dementia.
  • the inventors of the present invention confirmed that the decrease in the copy score of the Rey Complex Figure Test was greater when a single nucleotide polymorphism (SNP) that specifically appears in the onset of Alzheimer's disease was expressed, utilizing the genome-wide association study (GWAS) methodology, and completed the present invention.
  • SNP single nucleotide polymorphism
  • One aspect of the present invention relates to a genetic sample obtained from a patient
  • a method for providing information for predicting the risk of developing Alzheimer's disease comprising the step of identifying a single nucleotide polymorphism (SNP) represented by rs150908390.
  • SNP single nucleotide polymorphism
  • the above genetic sample refers to DNA or RNA that can be isolated from any cell of the subject (patient), including blood, skin cells, mucosal cells, and hair.
  • the method for extracting DNA or RNA from the cells is not particularly limited, and any technique known in the art or a commercially available DNA or RNA extraction kit can be used.
  • the subject (patient) above may include a subject diagnosed with or suspected of having Alzheimer's disease.
  • the subject may be a vertebrate, mammal, amphibian, reptile, bird, etc., and may specifically be a mammal.
  • the subject may be a human (Homo sapiens).
  • the term “gene” may be used interchangeably with the terms “polynucleotide” and “nucleic acid.”
  • the term “gene” refers to a DNA segment involved in the production of a polypeptide chain, and may include regions preceding and following a coding region, such as a promoter and a 3'-untranslated region, as well as intervening sequences (introns) between individual coding segments (exons).
  • genetic polymorphism refers to a case where two or more alleles exist at a single genetic locus, and a case where a genetic variation appears at a frequency of at least 1% or more in a population. Genetic polymorphism is distinguished from mutation, and genetic polymorphism refers to a case where a genetic variation appears at a frequency of at least 1% or more in a population, and a genetic variation found at a frequency lower than 1% is collectively called a mutation.
  • An insertion, deletion, or substitution of a single nucleotide in DNA is called a single nucleotide polymorphism (SNP).
  • single nucleotide polymorphism refers to a variation in DNA sequence that occurs when a single base (A, T, C, or G) in the genome differs between members of a species or between pairs of chromosomes of an individual. For example, in a certain region of the DNA chain, some people have adenine (A), while others have cytosine (C). These slight differences (SNPs) can alter the function of each gene, and these interact to create different individuals and differences in susceptibility to different diseases. In general, almost all SNPs have two alleles. Within a population, a SNP can be assigned a minor allele frequency (MAF; the lowest allele frequency at a locus found in a particular population). A single nucleotide can be changed (substituted), removed (deleted), or added (inserted) to a polynucleotide sequence. SNPs can cause a change in the translation frame.
  • a single base A, T, C, or G
  • C cytosine
  • [base letter/base letter] means that the base letter written on the left is replaced with the base letter written on the right .
  • polynucleotide or “nucleic acid” refers to deoxyribonucleotides (DNA) or ribonucleotides (RNA) in single- or double-stranded form. Unless otherwise specified, known analogs of naturally occurring nucleotides that hybridize to nucleic acids in a manner similar to naturally occurring nucleotides are also included.
  • DNA is generally composed of four bases: adenine (A), guanine (G), cytosine (C), and thymine (T), while RNA has uracil (U) instead of thymine.
  • 'polynucleotide means a polynucleotide having a contiguous base sequence of 8 to 100 nucleotides including the SNP of the present invention in the genomic region where the SNP is located.
  • genomic DNA means DNA that contains almost complete genetic information, which is the total base sequence of the genes of an individual.
  • risk of onset or “likelihood of onset” may mean the relative risk of onset of Alzheimer’s disease, and specifically may mean the likelihood of progressing to Alzheimer’s disease.
  • prediction may mean not only determining the possibility of developing Alzheimer’s disease by confirming the presence or characteristics of a pathological condition, but also determining whether there is drug responsiveness, resistance, etc. after Alzheimer’s disease treatment.
  • the above information providing method can be usefully utilized to predict the risk of developing Alzheimer's disease in Koreans.
  • the fact that the single nucleotide polymorphism marker can be used to predict the risk of developing Alzheimer's disease is based on the fact that the genetic analysis results of a group that developed Alzheimer's disease showed a high probability of the presence of a specific base at a single nucleotide polymorphism site.
  • compositions for predicting the risk of developing Alzheimer's disease comprising a polynucleotide consisting of 10 or more consecutive bases including a single nucleotide polymorphism (SNP) represented by rs150908390 or a polynucleotide that specifically hybridizes with its complementary polynucleotide.
  • SNP single nucleotide polymorphism
  • the polynucleotide composed of 10 or more consecutive bases according to the present invention or its complementary polynucleotide may include a polynucleotide composed of 10 or more consecutive bases, preferably 10 to 100, more preferably 20 to 80, and even more preferably 40 to 60, or a polynucleotide that specifically hybridizes with the polynucleotide or its complementary polynucleotide, but is not limited thereto.
  • the polynucleotide that specifically hybridizes with the polynucleotide described above may be a probe or a primer.
  • primer refers to an oligonucleotide, which can act as an initiation point for synthesis under conditions that induce the synthesis of a primer extension product complementary to a nucleic acid chain (template), i.e., the presence of nucleotides and a polymerization agent such as DNA polymerase, and conditions of suitable temperature and pH.
  • template i.e., the presence of nucleotides and a polymerization agent such as DNA polymerase, and conditions of suitable temperature and pH.
  • the primer is a deoxyribonucleotide and may be single-stranded.
  • the primer used in the present invention may include naturally occurring dNMPs (i.e., dAMP, dGMP, dCMP, and dTMP), modified nucleotides, or non-natural nucleotides.
  • the primer may also include ribonucleotides.
  • probe means a linear oligomer having a natural or modified monomer or linkage comprising deoxyribonucleotides and ribonucleotides capable of hybridizing to a specific nucleotide sequence.
  • the probe may be single-stranded for maximum efficiency in hybridization.
  • the probe may be a deoxyribonucleotide.
  • a sequence perfectly complementary to the sequence including the SNP may be used, but a substantially complementary sequence may also be used as long as it does not interfere with specific hybridization.
  • a probe not used in the present invention includes a sequence capable of hybridizing to a sequence including 10 to 30 consecutive nucleotide residues including the SNP of the present invention. More preferably, the 3' end or 5' end of the probe may have a base complementary to the SNP base.
  • the present invention provides a composition for predicting the risk of developing Alzheimer's disease, comprising a polypeptide encoded by the polynucleotide or an antibody specific therefor.
  • the process may begin with a step of amplifying or hybridizing a polymorphic site corresponding to the sequence represented by rs150908390 with a probe.
  • Any method known in the art can be used for the step of amplifying or hybridizing the polymorphic site with a probe.
  • the method may be a method of amplifying a target nucleic acid via PCR and purifying it.
  • the above method may be used, such as ligase chain reaction (LCR) (Wu and Wallace, Genomics 4, 560 (1989), Landegren et al., Science 241, 1077 (1988)), transcription amplication (Kwoh et al., Proc. Natl. Acad. Sci. USA 86, 1173 (1989)), self-sustaining sequence replication (Guatelli et al., Proc. Natl. Acad. Sci. USA 87, 1874 (1990)), or nucleic acid-based sequence amplification (NASBA).
  • LCR ligase chain reaction
  • LCR
  • the step of confirming the presence or absence of the mutation includes, but is not limited to, sequence analysis, hybridization by microarray, allele specific PCR, dynamic allele specific hybridization (DASH), PCR extension analysis, SSCP, PCR-RFLP analysis or TaqMan technique, SNPlex platform (Applied Biosystems), mass spectrometry (e.g., Sequenom's MassARRAY system), mini-sequencing method, Bio-Plex system (BioRad), CEQ and SNPstream system (Beckman), Molecular Inversion Probe array technology (e.g., Affymetrix GeneChip), and BreadArray technology (e.g., Illumina GoldenGate and Infinium assays).
  • sequence analysis hybridization by microarray, allele specific PCR, dynamic allele specific hybridization (DASH), PCR extension analysis, SSCP, PCR-RFLP analysis or TaqMan technique
  • SNPlex platform Applied Biosystems
  • mass spectrometry e.g., Sequenom's Mass
  • One or more alleles of a polymorphic marker can be identified using the above methods or other methods available to those skilled in the art to which the present invention pertains. Determining the base pairs of such polymorphic sites can preferably be performed using a SNP chip.
  • sequence analysis can be performed using any method known in the art.
  • the sequence analysis can be performed using an automatic sequencer, or can be performed using at least one method selected from known methods such as pyrosequencing, PCR-RELP (restriction fragment length polymorphism), PCR-SSCP (single strand conformation polymorphism), PCR-SSO (specific sequence oligonucleotide), ASO (allele specific oligonucleotide) hybridization combining PCR-SSO and dot hybridization, TaqMan-PCR, MALDI-TOF/MS, RCA (rolling circle amplification), HRM (high resolution melting), primer extension, Southern blot hybridization, or dot hybridization.
  • Another aspect of the present invention is a microarray for predicting the risk of developing Alzheimer's disease, comprising: a polynucleotide consisting of 10 or more consecutive bases including a single nucleotide polymorphism (SNP) represented by rs150908390 or a complementary polynucleotide thereof; a polynucleotide hybridizing therewith; a polypeptide encoded thereby; an antibody specific therefor; or cDNA of the polypeptide.
  • SNP single nucleotide polymorphism
  • the present invention provides a microarray for predicting the risk of developing Alzheimer's disease, comprising the polynucleotide, a polynucleotide hybridizing therewith, a polypeptide encoded thereby, an antibody specific therefor, or cDNA of the polypeptide.
  • the microarray according to the present invention may comprise DNA or RNA polynucleotides.
  • the microarray may be a conventional microarray, except that the probe polynucleotide comprises the polynucleotide of the present invention.
  • Methods for manufacturing a microarray by immobilizing the probe polynucleotide on a substrate are well known in the art.
  • the probe polynucleotide refers to a hybridizable polynucleotide, and refers to an oligonucleotide capable of sequence-specific binding to complementary strands of nucleic acids.
  • the probe of the present invention is an allele-specific probe, which means that a polymorphic site exists in nucleic acid fragments derived from two members of the same species, such that it hybridizes to a DNA fragment derived from one member but not to a fragment derived from the other member.
  • the hybridization conditions must be sufficiently stringent to ensure that the probe exhibits a significant difference in hybridization intensity between alleles and hybridizes to only one of the alleles. This can induce a favorable hybridization difference between different allelic forms.
  • the above diagnostic methods include detection methods based on nucleic acid hybridization, such as Southern blot, and in methods using DNA chips, the detection method may be provided in a form pre-bound to the DNA chip substrate.
  • the above hybridization can usually be performed under stringent conditions, such as a salt concentration of 1 M or less and a temperature of 25°C or higher.
  • the term "antibody” refers to a specific protein molecule directed against an antigenic site, a term well known in the art.
  • the antibody refers to an antibody that specifically binds to a polypeptide comprising the SNP marker of the present invention.
  • Such antibodies can be produced by conventional methods, such as cloning each gene into an expression vector to obtain a protein encoded by the marker gene, and producing the obtained protein using conventional methods.
  • This also includes partial peptides that can be produced from the protein, and the partial peptides of the present invention include at least 7 amino acids, preferably 9 amino acids, and more preferably 12 or more amino acids.
  • the form of the antibody of the present invention is not particularly limited, and polyclonal antibodies, monoclonal antibodies, or any antibody having antigen binding properties, as well as portions thereof, can be included in the antibody of the present invention, and all immunoglobulin antibodies can be included. Furthermore, the antibody of the present invention can also include specialized antibodies, such as humanized antibodies.
  • the antibody used for detecting the marker for predicting the risk of developing Alzheimer's disease of the present invention may include a complete form having two full-length light chains and two full-length heavy chains, as well as a functional fragment of the antibody molecule.
  • a functional fragment of an antibody molecule means a fragment that possesses at least an antigen-binding function, and may be Fab, F(ab'), F(ab') 2 , or Fv.
  • kits for predicting the risk of developing Alzheimer's disease comprising: a polynucleotide consisting of 10 or more consecutive bases including a single nucleotide polymorphism (SNP) represented by rs150908390 or a complementary polynucleotide thereof; a polynucleotide hybridizing therewith; a polypeptide encoded thereby; an antibody specific therefor; or cDNA of the polypeptide.
  • SNP single nucleotide polymorphism
  • the present invention provides a kit for predicting the risk of developing Alzheimer's disease, comprising the polynucleotide, a polynucleotide hybridizing therewith, a polypeptide encoded thereby, an antibody specific therefor, or cDNA of the polypeptide.
  • the kit may be a DNA chip, an RT-PCR kit, or a protein chip kit, but is not limited thereto.
  • the above kit can predict the risk of developing Alzheimer's disease by confirming through amplification of a SNP polymorphism marker, which is a marker for predicting the risk of developing Alzheimer's disease, or by confirming the expression level of the SNP polymorphism marker at the level of DNA or mRNA.
  • the kit for measuring the mRNA expression level of the marker for predicting the risk of developing Alzheimer's disease may be a kit including essential elements required for performing RT-PCR.
  • the RT-PCR kit may include a test tube or other appropriate container, a reaction buffer (with various pH and magnesium concentrations), deoxynucleotides (dNTPs), an enzyme such as Taq polymerase and reverse transcriptase, DNase, RNase inhibitor, DEPC water, sterile water, etc.
  • dNTPs deoxynucleotides
  • the kit according to the present invention may be a kit for predicting the risk of developing Alzheimer's disease, which includes the essential elements necessary for performing a DNA chip.
  • a DNA chip kit is a tool in which nucleic acid species are attached in a gridded array to a flat solid support, typically a glass surface no larger than a microscope slide, so that the nucleic acids are uniformly arranged on the chip surface, thereby allowing multiple hybridization reactions to occur between the nucleic acids on the DNA chip and complementary nucleic acids contained in a solution treated on the chip surface, thereby enabling massive parallel analysis.
  • the kit according to the present invention may be a protein chip kit.
  • the protein chip kit can measure the expression level of a protein composed of a mutated amino acid sequence.
  • the protein chip kit may include a substrate for immunological detection of an antibody, an appropriate buffer solution, a secondary antibody labeled with a chromogenic enzyme or fluorescent substance, a chromogenic substrate, etc.
  • the chromogenic enzyme may be peroxidase, alkaline phosphatase, etc. Additionally, FITC, RITC, etc. can be used as fluorescent materials, and AVTS (2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid)), OPD (o-phenylenediamine), TMB (tetramethyl benzidine), etc. can be used as chromogenic substrates.
  • the kit of the present invention manufactured as described above, is very economical compared to conventional general genetic mutation detection methods, as it saves time and money.
  • conventional genetic mutation detection methods such as SSCP (Single Strand Conformational Polymorphism), PTT (Protein Truncation Test), cloning, and direct sequencing
  • SSCP Single Strand Conformational Polymorphism
  • PTT Protein Truncation Test
  • cloning and direct sequencing
  • NGS next generation sequencing
  • RFLP Restriction Fragment Length Polymorphism
  • kits of the present invention if sample DNA is prepared, results can be obtained in about 10 to 11 hours, and since a set of primers capable of detecting mutations is integrated into a single chip, not only time but also cost can be saved compared to conventional methods. Since the average reagent cost per experiment is less than half that of conventional methods, even greater cost savings can be expected when considering the researcher's labor costs.
  • the present invention relates to a set of SNP genes, a composition, a method for providing information, and a kit capable of predicting the risk of developing Alzheimer's disease.
  • SNP variations associated with the risk of developing Alzheimer's disease were identified through genome-wide association analysis (GWAS), and the SNP variations can be utilized to diagnose or predict the onset of Alzheimer's disease in Koreans.
  • GWAS genome-wide association analysis
  • Figure 1 is a graph showing the Manhattan plot results for SNPs associated with Alzheimer's disease.
  • Figure 2 is a graph showing the regional plot of rs150908390, which is located on chromosome 11 and between the DDX10 gene and C110rf87.
  • Figure 3 is a mean profile plot graph showing the copy score measured over time for rs150908390.
  • Figure 4 is a survival curve analyzing the effect of the rs150908390 mutation and the onset of Alzheimer's disease over time.
  • the study sample included 1,325 subjects enrolled in cohorts at Chosun University and Chonnam National University who had completed the Rey Complex Figure Test at least twice.
  • Clinical diagnosis of Alzheimer's disease (AD) status was made according to the NINCDS-ADRDA (National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer Disease and Research Disorders Association) criteria.
  • Cognitively normal (CN) subjects had no evidence of neurological disease or impairment in cognitive function or activities of daily living. Subjects with a history of brain MRI, head trauma, or a history of psychiatric disorders that could affect mental function were excluded. At baseline, there were 50 cognitively normal (CN) subjects, 432 subjects with mild cognitive impairment (MCI), and 43 subjects with Alzheimer's disease (AD). The final sample included 775 controls.
  • LMM linear mixed model
  • Manhattan plots are used to identify and display statistically significant SNPs in GWAS.
  • the x-axis of the Manhattan plot is a visual diagram that displays the statistical value, i.e., the p-value , of each SNP as a scatter plot according to the SNP's location in the genome. If this shows an association with a phenotype, SNPs that show significance above or near the threshold at the corresponding locus may appear in groups.
  • SNPs with a p-value of 5x10-8 or less above the red line, p-value ⁇ 5x10-8 ) were identified, and these SNPs can be interpreted as having statistical significance (Figure 1).
  • age_i Age of the i-th subject
  • the verified SNP was rs150908390, and the regional plot showed that it was located on chromosome 11, between the DDX10 gene and C110rf87, and the location was 109121231 based on GRCh37.p13 (109250504 based on GRCh38.p14) (Fig. 2).
  • the x-axis represents the time (years) from one measurement to the next, and the y-axis represents the copy score.
  • the decline in RCFT copy score was significantly greater in subjects with the rs150908390 variant (Carrier, red on the graph) than in subjects without the variant (Non-Carrier, light blue on the graph) (Fig. 3).
  • rs150908390 analyzed using the NIH reference panel (GRCh37.p13) was confirmed to have the A genotype as the majority allele and the G genotype as the minor allele, and the frequency of the minor allele (maf) was 0.027.

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Abstract

La présente invention concerne : un procédé de génération d'informations permettant un diagnostic précoce et la prédiction de groupes présentant un risque de développer la maladie d'Alzheimer en utilisant des marqueurs SNP pouvant prédire un risque élevé de développer la maladie d'Alzheimer chez les Coréens ; une composition permettant de prédire le risque de développer la maladie d'Alzheimer ; une biopuce et un kit, chacun de ces éléments les comportant.
PCT/KR2024/018860 2024-01-30 2024-11-26 Marqueur de polymorphisme mononucléotidique associé à une réduction du score de copie de figure complexe de rey pour prédire le risque de développer la maladie d'alzheimer et son utilisation Pending WO2025164902A1 (fr)

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