Genetic Polymorphisms Associated With CAD
12 septembre 2017 mis à jour par: Interleukin Genetics, Inc.
Genetic Polymorphisms Associating With CAD, Inflammatory Biomarkers, and Oxidized Phospholipids in a Greek Population
The design and purpose of the current study is to expand and validate previous findings that the IL-1 gene cluster composite genotype patterns potentiate the risk for coronary artery disease (CAD) and cardiovascular events mediated by OxPL and Lp(a).
A secondary objective is to validate other, non IL-1 genetic variants associated with CAD.
Aperçu de l'étude
Statut
Inconnue
Les conditions
Intervention / Traitement
Description détaillée
The conclusions from an earlier study indicate that the contribution of OxPL/apoB and Lp(a) on angiographically documented CAD and CAD events is conditional on proinflammatory IL-1 genotypes.
This novel paradigm links the etiology of atherogenesis attributed to OxPL and Lp(a) from genetics to clinical expression of CAD.
ILI has also identified the functional IL-1 gene variations that regulate the IL1B gene in a haplotype context and appear to explain over-expression of IL-1β, as well as the expression of other inflammatory biomolecules that are downstream of IL-1β.
The functional IL-1 variants have been combined into patterns that have been associated with risk for more severe periodontal disease across multiple ethnic/racial populations.
It is also important to test this functional genetic pattern for similar interactions with OxPL and Lp(a) biomarker levels in association with angiographically documented CAD and CAD events.
DNA has been extracted from previously obtained subject blood samples (1173 subjects; 18 years to 90 years at entry (coronary angiography)) at the University General Hospital of Ioannina, Greece study site.
DNAs will be labeled by anonymized subject ID # (de-identified), and shipped to ILI for genotyping and genetic analysis.
Phase II will determine whether other gene variations (SNPs) previously shown in the literature to be associated with CAD and/or CAD-related secondary events can be validated in this study population.
Type d'étude
Observationnel
Inscription (Réel)
1173
Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans à 90 ans (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
Méthode d'échantillonnage
Échantillon de probabilité
Population étudiée
Patients between 18 years to 90 years at entry (coronary angiography) of both genders.
Patients with a previous history of coronary revascularization procedure or moderate to severe stenosis will be excluded.
Diabetics and non-diabetics, with or without known CV disease, who are admitted in the Department of Cardiology in the University General Hospital of Ioannina and the Catheterization Laboratory of 1st IKA Hospital in Athens and undergo coronary angiography for clinical purposes will be studied.
The study includes subjects who; 1) have suspected CAD and undergo a scheduled diagnostic angiogram for clinical reasons, and 2) are hospitalized because of an acute coronary syndrome and thus undergo diagnostic angiography (with or without previous history of CAD).
La description
Inclusion Criteria: Diabetics and non-diabetics, with or without known CV disease, who are admitted in the Department of Cardiology in the University General Hospital of Ioannina and the Catheterization Laboratory of 1st IKA Hospital in Athens and undergo coronary angiography at ages 18-90 for clinical purposes will be studied. The study includes subjects who; 1) have suspected CAD and undergo a scheduled diagnostic angiogram for clinical reasons, and 2) are hospitalized because of an acute coronary syndrome and thus undergo diagnostic angiography (with or without previous history of CAD).
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Exclusion Criteria: Patients < 18 years old and > 90 years old at time of coronary angiography. Patients with a previous history of coronary revascularization procedure or moderate to severe stenosis will be excluded.
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Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
Intervention / Traitement |
|---|---|
|
Case
Diabetic patients undergoing coronary angiography (both sexes), who are age 18-90, and admitted in the Department of Cardiology in the University General Hospital of Ioannina and Catheterization Laboratory of 1st IKA Hospital in Athens and undergo coronary angiography for clinical purposes will be studied.
Presence epicardial vessel stenosis (>50%), and multi-vessel disease will be recorded.
Excluded: previous history of revascularization procedure or moderate to severe stenosis.
Patient samples will be evaluated for quantitative levels of the biomarkers Lp(a) and OXPL/apoB.
IL-1 Genotypes, and other SNPs associated with CAD will be assessed in this group and related to levels of Lp(a) and oxidized phospolipids.
No interventions other than the post-hoc DNA testing will be performed.
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Genotyping will be carried out by a CLIA-certified genotyping facility at ILI, Waltham MA.
DNA concentrations will be adjusted to a range compatible with multiple PCR conditions.
Genotyping will be accomplished by performing multiplex polymerase chain reactions (PCR) specifically targeting the surrounding sequences for the SNPs being studied.
A single base extension assay will be hybridized to a 48-plex microarray plate and read on a SNPstream Genotyping System (Beckman-Coulter).
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Control
Non-diabeticpatients undergoing coronary angiography (both sexes), who are age 18-90, and admitted in the Department of Cardiology in the University General Hospital of Ioannina and Catheterization Laboratory of 1st IKA Hospital in Athens and undergo coronary angiography for clinical purposes will be studied.
Presence epicardial vessel stenosis (>50%), and multi-vessel disease will be recorded.
Excluded: previous history of revascularization procedure or moderate to severe stenosis.
Patient samples will be evaluated for quantitative levels of the biomarkers Lp(a) and OXPL/apoB.
IL-1 Genotypes, and other SNPs associated with CAD will be assessed in this group and related to levels of Lp(a) and oxidized phospolipids.
No interventions other than the post-hoc DNA testing will be performed.
|
Genotyping will be carried out by a CLIA-certified genotyping facility at ILI, Waltham MA.
DNA concentrations will be adjusted to a range compatible with multiple PCR conditions.
Genotyping will be accomplished by performing multiplex polymerase chain reactions (PCR) specifically targeting the surrounding sequences for the SNPs being studied.
A single base extension assay will be hybridized to a 48-plex microarray plate and read on a SNPstream Genotyping System (Beckman-Coulter).
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Evidence of IL-1 risk genotypes of the Heart Health Test in relation to levels of Lp(a)(mg/dL) and oxPL/apoB (RLU) in CAD patients.
Délai: Approximately 1 year
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Compare the frequencies of positive and negative genetic test results (Heart Health Test, composite genotype of rs17561, rs1143634, rs16944) among CAD patients based on previously collected levels (eg.
quartiles) of LP(a) and specific oxidized phospholipids among diabetic and non-diabetic subjects.
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Approximately 1 year
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Evidence of IL-1 risk genotypes of the PerioPredict Test in relation to levels of Lp(a)(mg/dL) and oxPL/apoB (RLU) in CAD patients.
Délai: Approximately 1 year
|
Compare the frequencies of positive and negative genetic test results (PerioPredict Test, composite genotype of rs16944, rs1143623, rs4848306, rs1143633)among CAD patients based on previously collected levels (eg.
quartiles) of LP(a) and specific oxidized phospholipids among diabetic and non-diabetic subjects.
|
Approximately 1 year
|
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Evidence for other non IL-1 gene SNPs, previously shown to be associated with CAD, in relation to levels of Lp(a)(mg/dL) and oxPL/apoB (RLU) among diabetic and non-diabetic patients.
Délai: Approximately 1 year
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Compare the frequencies of SNP alleles, haplotypes, and composite genotypes among CAD patients based on levels (eg.
quartiles) of LP(a) in mg/dL and oxidized phospholipids/apoB (RLU) among diabetic to non-diabetic subjects.
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Approximately 1 year
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Directeur d'études: Lynn Doucette-Stamm, Ph.D., Interleukin Genetics, Inc.
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 novembre 2014
Achèvement primaire (Anticipé)
1 novembre 2017
Achèvement de l'étude (Anticipé)
1 novembre 2017
Dates d'inscription aux études
Première soumission
21 novembre 2014
Première soumission répondant aux critères de contrôle qualité
1 décembre 2014
Première publication (Estimation)
4 décembre 2014
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
13 septembre 2017
Dernière mise à jour soumise répondant aux critères de contrôle qualité
12 septembre 2017
Dernière vérification
1 septembre 2017
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- ILI-14-133-C-UCSD
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
OUI
Description du régime IPD
Data will be shared with collaborators at University of California San Diego, La Jolla, California.
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