Genetic Polymorphisms Associated With CAD
2017年9月12日 更新者：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.
研究概览
详细说明
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.
研究类型
观察性的
注册 (实际的)
1173
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 90年 (成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
取样方法
概率样本
研究人群
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).
描述
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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学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
队列和干预
团体/队列 |
干预/治疗 |
|---|---|
|
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.
|
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.
|
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).
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
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.
大体时间：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
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
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.
大体时间：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.
大体时间：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.
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Approximately 1 year
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 研究主任：Lynn Doucette-Stamm, Ph.D.、Interleukin Genetics, Inc.
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2014年11月1日
初级完成 (预期的)
2017年11月1日
研究完成 (预期的)
2017年11月1日
研究注册日期
首次提交
2014年11月21日
首先提交符合 QC 标准的
2014年12月1日
首次发布 (估计)
2014年12月4日
研究记录更新
最后更新发布 (实际的)
2017年9月13日
上次提交的符合 QC 标准的更新
2017年9月12日
最后验证
2017年9月1日
更多信息
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