Genetic Polymorphisms Associated With CAD
- Conditions
- Coronary Artery Disease
- Interventions
- Genetic: IL-1 Genotypes, other SNPs associated with CAD
- Registration Number
- NCT02307422
- Lead Sponsor
- Interleukin Genetics, Inc.
- Brief Summary
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.
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 1173
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).
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.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Case IL-1 Genotypes, other SNPs associated with CAD 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. Control IL-1 Genotypes, other SNPs associated with CAD 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.
- Primary Outcome Measures
Name Time Method 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. 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.
- Secondary Outcome Measures
Name Time Method 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. 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.
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. 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.