Microarray Analysis of Gene Expression Signatures in Blood Samples Provides Biomarker for Higher Cardiovascular Death Risk

Differences in gene expression have been found among a population of coronary artery disease (CAD) patients that seemed to indicate which of them were at higher risk of dying from the illness.

Investigators at the Georgia Institute of Technology (Atlanta, USA) and colleagues at Emory University (Atlanta, GA, USA) and Princeton University (Princeton, NJ, USA) examined whether gene expression profiles obtainable from peripheral blood could be predictive of acute myocardial infarction (AMI) and/or cardiovascular death.

They analyzed blood samples from 338 CAD subjects (220 males, 118 females) aged from 51 to 73 years and monitored them over a period of 2.4 years for cardiovascular death. Gene expression was measured using Illumina (San Diego, CA, USA) HT-12 microarrays.

Illumina HumanHT-12 v4 Expression BeadChip microarrays provide genome-wide transcriptional coverage of well-characterized genes, gene candidates, and splice variants, delivering high-throughput processing of 12 samples per BeadChip without the need for expensive, specialized automation. Each array on the HumanHT-12 v4 Expression BeadChip targets more than 47,000 probes derived from the National Center for Biotechnology Information Reference Sequence and other sources. HumanHT-12 Expression BeadChips use the Direct Hybridization Assay and are scanned on the HiScan or iScan systems.

Results of the study revealed that there was significant differential gene expression between healthy and AMI groups with overall down-regulation of genes involved in T-lymphocyte signaling and up-regulation of inflammatory genes. During the follow-up period 31 patients died of CAD. Gene analysis of these individuals yielded covariance of 238 genes that were differentially expressed between deceased and survivors that significantly predicted risk of cardiovascular death.

"What is new in this research is the recognition that this risk pathway exists and that it relates to particular aspects of immune system functions that include T-cell signaling," said senior author Dr. Gregory Gibson, professor of biology at the Georgia Institute of Technology. "We went beyond the signature of coronary artery disease to really provide a signature for adverse outcomes in that high-risk population. We envision that with our gene expression-based marker, plus some biochemical markers, genotype information, and family history, we could produce a tiered evaluation of people's risks of adverse coronary events. This could lead to a personalized medicine approach for people recovering from heart attack or coronary artery bypass grafting."

"Our dream would be a hand-held device that would allow patients to take a droplet of blood, much like diabetics do today, and obtain an evaluation of these transcripts that they could track at home," said Dr. Gregory. "If we can use this information to help people adopt healthier behaviors, it will be very positive."

The CAD gene expression study was published in the May 30, 2014, online edition of the journal Genome Medicine.

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Georgia Institute of Technology
Emory University
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