Findings Also Show No Significant Difference from Earlier Published Reports by Celera and Others on Case-Control Studies of KIF6
ALAMEDA, Calif.--(BUSINESS WIRE)-- Celera Corporation (NASDAQ:CRA) today noted that the case-control studies describing a lack of association between KIF6 and coronary artery disease (CAD) published in the Journal of the American College of Cardiology did not investigate the association between KIF6 and statin benefit and the results are subject to fundamental biases that limit any comparison to the previous prospective studies that found an association between KIF6 and coronary heart disease (CHD).
“We believe that the case-control study of coronary artery disease published by Assimes et al., is not a replication study of the published prospective studies of KIF6 Trp719Arg, which involved rigorous prospective and randomized controlled trial designs,” said Thomas White, Ph.D., Chief Scientific Officer at Celera. ”Moreover, Celera and others have previously reported1-4 the finding that in case-control studies there was no association between KIF6 and nonfatal MI or CAD, and thus we see little that is new or relevant to the association between KIF6 and statin benefit.”
Genetic studies of four randomized controlled clinical trials (CARE, WOSCOPS, PROVE IT, and PROSPER) found that statin treatment significantly reduced CHD events in carriers of the KIF6 variant. Celera notes that the investigators of these latest case-control studies speculate that statin use was not common enough to have suppressed an association between the KIF6 variant and CAD in the case-control studies. However, if KIF6 carriers taking statins had benefited from therapy, they would not have been included among the CAD cases in these studies – thereby reducing the possibility of finding an association between KIF6 and risk for CAD. Simply put, the prevalence of statin use was not reliably known by the authors of the case-control studies - unlike in the rigorously controlled randomized trials cited above in which the KIF6 variant was studied. Indeed, the Assimes et al., paper even notes the lack of robust awareness of traditional risk factors in the case-control studies. Similarly, other reports have convincingly demonstrated that case-control studies of the association of hypertension with risk “are seriously compromised when the trait is subject to the effects of anti-hypertensive treatment5.”
“We believe this case-control publication mischaracterizes the prior peer-reviewed papers on KIF6’s association with CHD. To ascribe more credence to results from case-control studies, with their long history of known selection biases than to results from prospective cohort studies and prospective, placebo-controlled, randomized clinical trials, runs counter to the accepted hierarchy of medical evidence. Additionally, 70% of the CAD samples used in the Assimes et al., case-control study publication and multiple co-authors of the paper are employed by a commercial firm that sells a competing genetic test for CHD risk,” added Dr. White.
The accompanying editorial, which contains numerous inaccuracies, misstatements and omissions, wrongly asserts that the prior KIF6 results “stems primarily from a few observational studies” and inaccurately states that the reports of CHD event reduction from statin therapy in KIF6 carriers are “largely unsubstantiated”. In fact, a combined analysis of 7 large prospective studies has demonstrated the association between KIF6 and CHD risk6. Further, the association between KIF6 and statin benefit was established in genetic studies of four randomized, controlled clinical trials (CARE, WOSCOPS, PROVE IT, and PROSPER) in which statin therapy was found to reduce CHD events in carriers of the KIF6 variant. Thus, the KIF6 gene variant has been investigated in studies that included a total of approximately 55,000 people. The statistical analyses reported for five of these studies were conducted by external academic groups.
Research supporting KIF6
The association between KIF6 and event reduction during pravastatin (Pravachol®) therapy has been demonstrated previously in three prospective, placebo-controlled randomized clinical trials of statin therapy for the prevention of CHD events: the secondary prevention Cholesterol and Recurrent Events (CARE) study; the primary prevention West of Scotland Coronary Prevention Study (WOSCOPS); and the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study. Additionally, a genetic study of PROVE IT―TIMI 22 reported that in patients who experienced an acute coronary syndrome (ACS), high-dose atorvastatin (Lipitor®), compared with standard dose pravastatin, was significantly more effective at reducing CHD events in KIF6 carriers than in noncarriers. To date, a differential benefit of statin therapy for KIF6 carriers versus noncarriers has only been reported for atorvastatin and pravastatin therapy. A published abstract suggests that noncarriers may benefit from simvastatin therapy.
The KIF6 gene variant has also been reported to predict risk of CHD in prospective population cohort studies. This gene variant was associated with increased risk of CHD in Caucasian and African American participants of the Atherosclerosis Risk in Communities (ARIC) study of 13,907 middle aged Americans, and with increased risk for myocardial infarction (MI) in both the Cardiovascular Health Study of 4,522 Americans, aged 65 or older, and the Women’s Health Study of 25,283 women older than 45 years and without a previous history of CHD.
The increased risk of CHD events observed in KIF6 carriers has been shown to be independent of other well-known CHD risk factors, including smoking, hypertension, cholesterol level, age, and sex, further supporting the conclusion that the KIF6 gene variant is an independent predictor of risk for CHD. In a presentation at the 2010 Arteriosclerosis, Thrombosis, and Vascular Biology meeting of the American Heart Association, the KIF6 protein was also reported to be expressed in atherosclerotic lesions in both mouse and human arteries but not in normal arteries, adding supporting biological information to the genetic results.
Celera is a healthcare business focusing on the integration of genetic testing into routine clinical care through a combination of products and services incorporating proprietary discoveries. Berkeley HeartLab, a subsidiary of Celera, offers services to predict cardiovascular disease risk and improve patient management. Celera also commercializes a wide range of molecular diagnostic products through Abbott and has licensed other relevant diagnostic technologies developed to provide personalized disease management in cancer. Information about Celera Corporation, including reports and other information filed by the company with the Securities and Exchange Commission, is available at http://www.celera.com.
Certain statements in this press release are forward-looking. These may be identified by the use of forward-looking words or phrases such as "believe," “intends,” "plan," and "could," among others. These forward-looking statements are based on Celera Corporation's current expectations. The Private Securities Litigation Reform Act of 1995 provides a "safe harbor" for such forward-looking statements. In order to comply with the terms of the safe harbor, Celera notes that a variety of factors could cause actual results and experience to differ materially from the anticipated results or other expectations expressed in such forward-looking statements. These factors include but are not limited to: (1) Celera’s scientific discoveries may not be replicated in studies by other investigators, which may negatively impact the acceptance of the Company’s diagnostic products and testing services; (2) Celera is using novel and unproven methods to discover markers for the development of new diagnostic products, which may not be successful; (3) the diagnostic industry is very competitive, and new diagnostic products may not be accepted and adopted by the market; (4) demand for diagnostic products may be adversely affected if users of these products cannot receive adequate reimbursement for these products from third party payors such as private insurance companies and government insurance plans; (5) potential product liability or other claims against Celera as a result of the testing or use of its products; and (6) uncertainty of the availability to Celera of intellectual property protection, limitations on its ability to protect trade secrets, the risk to it of infringement claims, and the possibility that it may need to license intellectual property from third parties to avoid or settle such claims. The foregoing list sets forth some, but not all, of the factors that could affect Celera's ability to achieve results described in any forward-looking statements. For additional information about the risks and uncertainties that Celera faces and a discussion of its financial statements and footnotes, see documents filed by Celera with the SEC, including its Annual Report on Form 10-K and all subsequent periodic reports. All information in this press release is as of the date of the release, and Celera does not undertake any duty to update this information, including any forward-looking statements, unless required by law.
1. Bare et al., PLoS ONE; 29 Sep 2010 10.1371
2. Shiffman et al., Am J Hum Genet 2005; 77:596-605.
3. Luke et al., Arterioscler Thromb Vasc Biol 2007; 27(9):2030-6.
4. Stewart et al., J Am Coll Cardiol 2009; 53:1471-2.
5. Tobin et al., Statis Med 2005; 24:2911-35.
6. Li et al., Am J Cardiol. 2010; 106:994-8.
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David Speechly, Ph.D., 510-749-1853
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INDUSTRY KEYWORDS: Health Biotechnology Cardiology Clinical Trials Genetics Pharmaceutical