Celera Presents Results Showing That Carriers Of An LPA Gene Variant Are At Elevated Risk Of CHD Among Non-Users Of Aspirin

Main Category: Heart Disease
Also Included In: Cardiovascular / Cardiology;  Genetics
Article Date: 03 May 2009 - 0:00 PDT

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Celera Corporation (NASDAQ:CRA) and its collaborators at The University of Texas, Baylor College of Medicine, and Brigham and Women's Hospital, reported that, among non-users of aspirin, those who carry an LPA gene variant were at increased risk of coronary heart disease (CHD), compared with noncarriers. Carriers of the LPA variant were not at increased risk among those who use aspirin. This study was conducted among the middle aged Caucasian men and women of the ARIC study. These results were presented today at the 2009 Arteriosclerosis, Thrombosis and Vascular Biology Annual Conference under the auspices of the American Heart Association in Washington, DC.

The current study is consistent with previous findings(1) from the Women's Health Study, a randomized trial of aspirin and placebo, where carriers of this LPA gene variant when compared with noncarriers, had over 2 fold increased risk for major cardiovascular events in the placebo group, an excess risk that was essentially eliminated by low-dose aspirin therapy.

Recent studies indicate that the LPA gene variant is a new, independent predictor of risk for CHD in men and women(2-4) and clinical benefit from aspirin therapy in women(1). LPA encodes apolipoprotein(a), a protein component of Lp(a) plasma lipoprotein particles, and the gene variant results in an amino acid substitution (methionine for isoleucine) in the protease-like domain of apolipoprotein(a). Approximately 3.5% of Caucasians in studied populations are carriers of the LPA gene variant, and these carriers have also been found to have higher levels of plasma Lp(a) levels.

Study Details

Findings from the current study were based on analysis of 6,752 Caucasian participants in the Atherosclerosis Risk in Communities (ARIC) Study, a large-scale, long-term prospective study that is being conducted to investigate established and suspected CHD risk factors in middle aged American men and women. During a median follow-up of 7.2 years after aspirin use information was collected, 636 (9.4%) of the participants in this study had a first incident CHD event. After adjusting for age and sex, the hazard ratio for CHD among 5,330 non-users of aspirin was 1.57 (for carriers of the LPA gene variant compared with noncarriers); the hazard ratio of 0.86 among 1,422 aspirin users.

"This study indicates that carriers of the LPA gene variant are both at higher risk of cardiovascular disease and that this risk is not observed among users of aspirin," said Eric Boerwinkle, Ph.D., Professor and Center Director, Human Genetics Center at the University of Texas, and senior author of the abstract. "These data could provide a genetic method for defining subpopulations with differential benefit from aspirin therapy for prevention of coronary heart disease."

"We believe this supporting evidence for our previous findings regarding the LPA gene variant in a population that includes aspirin treatment information in both men and women is an important step toward demonstrating the clinical utility among different segments of the population," said Thomas White, Ph.D., Chief Scientific Officer at Celera. "We believe these findings make a compelling case for testing for LPA status, and further our commitment to be a leading provider of genetic tests used routinely in personalizing disease management."

References

1. Chasman DI, Shiffman D, Zee RYL, et al. Polymorphism in the apolipoprotein(a) gene, plasma lipoprotein(a), cardiovascular disease, and low-dose aspirin therapy. Atherosclerosis, 2009; 203:371-6

2. Luke MM, Kane JP, Liu DM, et al. A polymorphism in the protease-like domain of apolipoprotein(a) is associated with severe coronary artery disease. Arterioscler Thromb Vasc Biol 2007; 27:2030-6.

3. Shiffman D, Kane JP, Louie JZ, et al. Analysis of 17,576 potentially functional SNPs in three case-control studies of myocardial infarction. PLoS ONE 2008; 3:e2895.

4. Shiffman D, O'Meara ES, Bare LA, et al. Association of gene variants with incident myocardial infarction in the cardiovascular health study. Arterioscler Thromb Vasc Biol. 2008; 28:173-9.

Source
Celera Corporation