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.
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
1,173
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).
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.
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.
Time frame: Approximately 1 year
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.
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.
Time frame: 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.
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.
Time frame: Approximately 1 year
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