Dataset Information

Genetic testing for atherosclerosis risk: inevitability or pipe dream?

ABSTRACT: Family history is a risk factor for coronary artery disease (CAD). However, defining this risk at the DNA level has been elusive. In 2007, four genome-wide association studies reported a strong association between CAD and a region on chromosome 9p21. The high-risk genotype was identified in up to 30% of individuals, creating the potential for a clinical genetic test to assist in the calculation of a patient's CAD risk. However, the reported effect size of the association is modest (OR of approximately 1.3). The present paper examines the feasibility of including DNA tests in CAD risk prediction algorithms. The greatest contribution from the 9p21 association is likely yet to come, as further studies identify the mechanistic basis for the association, possibly leading to additional insights into the progression, prevention and treatment of CAD.

SUBMITTER: Lanktree M

PROVIDER: S-EPMC2644538 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genetic testing for atherosclerosis risk: inevitability or pipe dream?

Lanktree Matthew M Oh Jisun J Hegele Robert A RA

The Canadian journal of cardiology 20081101 11

Family history is a risk factor for coronary artery disease (CAD). However, defining this risk at the DNA level has been elusive. In 2007, four genome-wide association studies reported a strong association between CAD and a region on chromosome 9p21. The high-risk genotype was identified in up to 30% of individuals, creating the potential for a clinical genetic test to assist in the calculation of a patient's CAD risk. However, the reported effect size of the association is modest (OR of approxi ...[more]

PMID: 18987759

Similar Datasets

Project description:Rationale: Epicardial adipose tissue (EAT) has been independently associated with non-calcified, high-risk coronary plaques in low-to intermediate risk subjects. Recently, a bidirectional communication was shown between EAT and diseased coronary arteries. In high-risk patients it is unknown whether quantitative measures of EAT can capture, and which molecular players are involved in this mutual interplay. Objective: In a high-risk population, we aimed to determine how the volume of EAT is linked to coronary artery disease (CAD) and to identify potential EAT-deregulated pathways in CAD patients specifically related to coronary artery calcification (CAC). Methods and Results: In a prospective cohort of 574 degenerative severe aortic stenosis patients referred to cardiac surgery, we quantified fat depots by computed tomography (CT) and performed a comparative quantitative proteomics of thoracic fat, including EAT, mediastinal (MAT) and subcutaneous (SAT) adipose tissues. We did not find an independent association of EAT volume with the severity, distribution and complexity of coronary stenosis in invasive coronary angiography. Although, EAT volume was correlated with high CAC, its cardiovascular risk factors-adjusted association was not significant. Taking as reference non-CAD matched-patients and compared to MAT and SAT, EAT proteomic signature of CAD was characterized by up-regulation of pro-calcifying annexins (Annexin A2, ANXA2), fatty acid binding transporters (FABP4) and inflammatory signaling proteins, and by down-regulation of fetuin-A and redox state regulatory enzymes. In EAT, ANXA2 regulation was positively correlated with CAC. EAT gene expression studies confirmed overexpression of ANXA2 and FABP4 in CAD, but no expression of FETUA was detected. Compared with non-CAD, fetuin-A circulating levels were higher in CAD, whereas no fetuin-A pericardial fluid differences were found. Conclusions: In this high-risk cohort, EAT presented an imbalance of pro-calcifying, pro-inflammatory and lipid transporters mediators. These local EAT-mediated regulatory mechanisms were not reflected by the CT volume of EAT alone.

Dataset Information

Genetic testing for atherosclerosis risk: inevitability or pipe dream?

Publications

Genetic testing for atherosclerosis risk: inevitability or pipe dream?

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets