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1. WO2021058597 - METHODS OF DETERMINING WHETHER A SUBJECT IS AT RISK OF DEVELOPING ARTERIAL PLAQUES

Publication Number WO/2021/058597
Publication Date 01.04.2021
International Application No. PCT/EP2020/076617
International Filing Date 23.09.2020
IPC
G16H 50/30 2018.01
GPHYSICS
16INFORMATION AND COMMUNICATION TECHNOLOGY SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
50ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
30for calculating health indices; for individual health risk assessment
C12Q 1/6883 2018.01
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
QMEASURING 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
1Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
68involving nucleic acids
6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
6883for diseases caused by alterations of genetic material
C12Q 1/37 2006.01
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
QMEASURING 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
1Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
34involving hydrolase
37involving peptidase or proteinase
CPC
C12Q 1/37
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS
1Measuring or testing processes involving enzymes, nucleic acids or microorganisms
34involving hydrolase
37involving peptidase or proteinase
C12Q 1/6883
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS
1Measuring or testing processes involving enzymes, nucleic acids or microorganisms
68involving nucleic acids
6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
6883for diseases caused by alterations of genetic material
C12Q 2600/156
CCHEMISTRY; METALLURGY
12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS
2600Oligonucleotides characterized by their use
156Polymorphic or mutational markers
G01N 2333/9643
GPHYSICS
01MEASURING; TESTING
NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
2333Assays involving biological materials from specific organisms or of a specific nature
90Enzymes; Proenzymes
914Hydrolases (3)
948acting on peptide bonds (3.4)
95Proteinases, i.e. endopeptidases (3.4.21-3.4.99)
964derived from animal tissue
96425from mammals
96427in general
9643with EC number
G16H 50/30
GPHYSICS
16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
50ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
30for calculating health indices; for individual health risk assessment
Applicants
  • INSERM (INSTITUT NATIONAL DE LA SANTÉ ET DE LA RECHERCHE MÉDICALE) [FR]/[FR]
  • UNIVERSITÉ DE LORRAINE [FR]/[FR]
  • CENTRE HOSPITALIER ET UNIVERSITAIRE DE NANCY (CHU) [FR]/[FR]
  • COMMISSARIAT À L'ÉNERGIE ATOMIQUE ET AUX ÉNERGIES ALTERNATIVES (CEA) [FR]/[FR]
Inventors
  • ROSSIGNOL, Patrick
  • LE FLOCH, Edith
  • DANDINE-ROULLAND, Claire
  • ZANNAD, Faiez
  • XHAARD, Constance
  • FERREIRA, João Pedro
  • DELEUZE, Jean-François
Agents
  • INSERM TRANSFERT
Priority Data
19306180.124.09.2019EP
Publication Language English (EN)
Filing Language English (EN)
Designated States
Title
(EN) METHODS OF DETERMINING WHETHER A SUBJECT IS AT RISK OF DEVELOPING ARTERIAL PLAQUES
(FR) PROCÉDÉS DE DÉTERMINATION DU RISQUE D'APPARITION DE PLAQUES ARTÉRIELLES CHEZ UN SUJET
Abstract
(EN)
Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds low-density lipoprotein receptor (LDLR), preventing its recycling. PCSK9 is a risk predictor and a biotarget in atherosclerosis progression. The aim of the inventors was to determine whether the PCSK9- LDLR axis can predict carotid artery plaques between two visits separated by almost 20 years in a longitudinal population cohort (i.e. STANISLAS cohort), and whether underlying genetic polymorphisms could be identified. Participants attending two visits (visit 1 and visit 4) separated by 18.5 years (mean) were included (n=997). The independent clinical predictors of arterial plaques were age, smoking and LDLc. Higher PCSK9 levels predicted arterial plaques on top of the clinical model, OR (95%CI) =2.14 (1.28-3.58); the missense mutation coding the single-nucleotide polymorphism (SNP) rs562556 is associated with both higher PCSK9 concentration and arterial plaques. In conclusion higher PCSK9 concentration predicted the development of arterial plaques almost 20 years in advance in a healthy middle-aged population. Mutations of the SNP rs562556 associated with both PCSK9 levels and arterial plaques reinforce the potential causality of the findings. Finally PCSK9 inhibitors would be useful for cardiovascular prevention in patients considering having risk of developing arterial plaques.
(FR)
La proprotéine convertase subtilisine/kexine de type 9 (PCSK9) se lie au récepteur des lipoprotéines de basse densité (LDLR), ce qui empêche son recyclage. PCSK9 est un prédicteur de risque et une biocible dans la progression de l'athérosclérose. Le but de la présente invention est de déterminer si l'axe PCSK9-LDLR peut permettre de prédire des plaques artérielles au niveau de la carotide entre deux visites séparées de presque 20 ans dans une cohorte de population longitudinale (cohorte STANISLAS) et si des polymorphismes génétiques sous-jacents pourraient être identifiés. Ont été inclus des participants (n = 997) s'étant rendus à deux visites (visite 1 et visite 4) séparées de 18,5 ans (moyenne). Les prédicteurs cliniques indépendants des plaques artérielles étaient l'âge, le tabagisme et le cholestérol LDL. Des niveaux de PCSK9 supérieurs ont permis de prédire la présence de plaques artérielles en quantité supérieure au modèle clinique, OR (95 % CI) = 2,14 (1,28-3,58) ; la mutation faux sens codant pour le polymorphisme mononucléotidique (SNP) rs562556 est associée à la fois à une concentration de PCSK9 supérieure et à des plaques artérielles. En conclusion, une concentration supérieure en PCSK9 a permis de prédire l'apparition de plaques artérielles presque 20 ans à l'avance chez une population d'âge moyen en bonne santé. Des mutations du SNP rs562556 associées aux niveaux de PCSK9 et aux plaques artérielles renforcent la causalité potentielle des découvertes. Enfin, les inhibiteurs de PCSK9 devraient être utiles pour la prévention cardiovasculaire chez les patients dont on considère qu'ils sont à risque de voir apparaître des plaques artérielles.
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