Genetic Polymorphisms Associated With CAD

September 12, 2017 updated by: 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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

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.

Study Type

Observational

Enrollment (Actual)

1173

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 90 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

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).

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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Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
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.
Genetic: IL-1 Genotypes, other SNPs associated with CAD
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).
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.
Genetic: IL-1 Genotypes, other SNPs associated with CAD
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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: Approximately 1 year
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.
Approximately 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Time Frame: 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
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.
Time Frame: Approximately 1 year
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.
Approximately 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Interleukin Genetics, Inc.

Collaborators

University of California, San Diego

Investigators

  • Study Director: Lynn Doucette-Stamm, Ph.D., Interleukin Genetics, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

November 1, 2014

Primary Completion (Anticipated)

November 1, 2017

Study Completion (Anticipated)

November 1, 2017

Study Registration Dates

First Submitted

November 21, 2014

First Submitted That Met QC Criteria

December 1, 2014

First Posted (Estimate)

December 4, 2014

Study Record Updates

Last Update Posted (Actual)

September 13, 2017

Last Update Submitted That Met QC Criteria

September 12, 2017

Last Verified

September 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ILI-14-133-C-UCSD

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Data will be shared with collaborators at University of California San Diego, La Jolla, California.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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