New Journal Focuses On Cardiovascular Genetics

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New research on gene expression patterns in people with blocked coronary arteries, genetic influences in determining blood levels of ‘bad’ and ‘good’ cholesterol, and the role of genes in abdominal aortic aneurysm are among the research highlighted in Circulation: Cardiovascular Genetics. The journal is the sixth new specialty journal that Circulation: Journal of the American Heart Association has launched recently.

“The content of this new journal will bridge the domains of congenital heart disease, adolescent and adult cardiac disorders, and aging-associated cardiovascular ailments,” said Editor Ramachandran S. Vasan, M.D.

The launch of Circulation: Cardiovascular Genetics represents “a small but important step” toward “practicing personalized preventive cardiovascular medicine,” Vasan said. “We are beginning to understand how genetic factors interact with environmental influences over an entire lifetime to pattern and remodel function at the molecular, cellular, tissue and organ levels that ultimately manifest as subclinical or clinical cardiovascular disease.”

The new journal will feature research from scientists invested in many different aspects of cardiovascular genetics and genomics (the identification and study of gene sequences in the DNA of organisms), including: clinical cardiologists, clinical and basic scientists, trialists, epidemiologists, geneticists, molecular biologists and ethicists.

Vasan hopes that Circulation: Cardiovascular Genetics will fulfill the need for a journal focused exclusively on investigations in cardiovascular genetics, genomics and other ‘Omics’ sciences (e.g., proteomics and metabolomics, specialties that investigate proteins and metabolites, respectively). “The education of the cardiologist in “genomics” tools and their clinical applications requires an army of teachers and investigators,” Vasan said.

Here are summaries of three featured reports among articles in the first issue:

Gene expression in circulating blood cells reflect presence, extent of coronary artery disease

In a group of patients undergoing coronary catheterization, researchers have found a pattern of gene expression in circulating blood cells that indicates the presence and extent of coronary artery disease (CAD). If validated in a large, multi-center clinical trial currently underway, the findings could lead to a blood-based molecular diagnostic test to diagnose CAD, which is the leading cause of death in the United States.

From a group of patients in a catheterization study the investigators identified 41 subjects — 27 with significant CAD and 14 controls without coronary artery narrowing. Researchers performed a whole genome microarray analysis on peripheral blood mononuclear cells (PBMC) and found 526 statistically significant genes with greater than a 1.3 fold change between patients with significant CAD and controls. A separate analysis on 106 genes in a subset of 95 subjects (63 cases, 32 controls) from the same catheterization study found 14 genes that were markers for CAD, even after controlling for clinical and demographic factors, the researchers said.

From a second group of 215 catheterization patients, the researchers selected a case/control subset of 107 patients (86 cases, 21 controls) and replicated their earlier results in 11 of the 14 genes from the first cohort. Analysis of the 14 genes in the 215 patients “demonstrated that gene expression was proportional to the degree of blockage of arteries (maximal coronary artery stenosis),” the researchers said. Thus, the study concludes, “Gene expression in peripheral blood cells reflects the presence and extent of CAD in patients undergoing angiography.”

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Chromosome variant that increases risk of CAD now linked to abdominal aortic aneurysm

Recent genome-wide studies have shown a significant association between a locus on chromosome 9p21.3 and coronary artery disease (CAD). Now, researchers have confirmed that this same locus is associated with abdominal aortic aneurysm.

In their study, 1,714 patients (899 patients with abdominal aortic aneurysm and 815 controls) were genotyped and researchers found “a significant association” between the C (risk) allele of a variant in the genetic locus and abdominal aortic aneurysm. Compared to the GG genotype, the GC genotype was associated with a 1.2 fold increased chance of having an abdominal aortic aneurysm and the CC genotype with a 1.5 fold increased chance. Logistic regression analysis showed the association of the CC genotype with abdominal aortic aneurysm was independent of the presence of clinical CAD.

From the findings, researchers conclude that the effect of this recently identified genetic locus — the chromosome 9 variant — on the risk of cardiovascular disease “extends beyond the coronary circulation.”

Genome-wide study points anew to emerging biological pathways governing lipid metabolism

Much of cardiovascular disease that cannot be explained by identifiable risk factors lies “in our genes.” Thus genetic pathways controlling lipid metabolism (normal and abnormal), are the subject of intense scrutiny by researchers seeking possible new strategies to develop better drugs to lower cholesterol levels and reduce the risk of developing heart attacks and strokes.

A genome-wide analysis among 6,382 Caucasian women and two additional groups totaling 970 women provided new insights into hidden tendencies tucked away in our DNA.

The researchers looked for associations between common SNPs (single nucleotide polymorphisms-DNA sequence variations that occur when a single nucleotide in the genome sequence is altered), and blood levels of LDL-C, HDL-C, triglycerides, ApoA1 and ApoB.

The study found associations with genome-wide statistical significance at the PCSK9 gene, APOB gene, LPL gene, APOA1-APOA5 locus, LIPC gene, CETP gene, LDLR gene and APOE locus. And associations were found with triglycerides, ApoA1, and ApoB at the GCKR gene that confirm and extend emerging links between glucose and lipid metabolism, researchers said.

Other connections (at the 1p13.3 locus) “are consistent with emerging biological properties for a region of the genome, possibly related to the SORTI gene or other neighboring genes,” researchers said. And further results below genome-wide significance confirm associations at five new loci with LDL-C, HDL-C or triglycerides reported in other recent genome studies.

“Genome-wide associations at the GCKR gene and at the 1p13.3 locus as well as confirmatory associations at five other novel loci suggest emerging biological pathways that influence lipid metabolism among Caucasian women,” researchers said.

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