CORRESPONDENCE: LETTER TO THE EDITOR
Association of the 719Arg Variant of KIF6 With Both Increased Risk of Coronary Events and With Greater Response to Statin Therapy
Olga Iakoubova, MD, PhD*,
James Shepherd, PhD and
Frank Sacks, MD
* Celera, Cardiovascular Diseases, 1401 Harbor Bay Parkway, Alameda, California 94502 (Email: olga.iakoubova{at}celera.com).
We read with interest the editorial comment (1) accompanying 3 reports that described the association of the 719Arg allele of KIF6 with both increased risk of coronary heart disease and with response to statin treatment (2–4). However, we would like to comment on 2 assertions made in that evaluation of the work. The editorial stated that KIF6 is not expressed in the vasculature. One would expect a gene with a biologically plausible role in coronary heart disease to be expressed in coronary arteries, and, in fact, KIF6 is expressed in coronary arteries and other vascular tissue. A striking example of KIF6 expression in human coronary arteries can be seen in the data generated by King et al. (5). Their data indicated that, in some human coronaries, KIF6 is among the top 5% of overexpressed genes, based on a study of over 20,000 genes (see GEO accession number GDS1597 at http://www.ncbi.nlm.nih.gov/projects/geo/).
The editorial also stated that the KIF6 association studies were restricted to analysis of only 1 single nucleotide polymorphism (SNP) in the KIF6 gene. In fact, Iakoubova et al. (2) reports an analysis of 26 additional SNPs in a 95.5-kb interval of Chr 6 that surrounds the KIF6 Trp719Arg SNP. These 26 additional SNPs could also be considered surrogates (or tagging SNPs) for 117 additional SNPs in this interval.
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Footnotes
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Please note: Dr. Iakoubova has employment and ownership interest for Celera; Dr. Shepherd is on the Speakers' Bureau for AstraZeneca, Pfizer, and Sankyo and is a consultant for AstraZeneca, Pfizer, and GlaxoSmithKline; and Dr. Sacks was an expert witness for Pfizer and is a consultant for Bristol-Myers Squibb.
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References
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- Marian AJ. Surprises of the genome and "personalized" medicine J Am Coll Cardiol 2008;51:456-458.[Free Full Text]
- Iakoubova OA, Tong CH, Rowland CM, et al. Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials: the CARE and WOSCOPS trials J Am Coll Cardiol 2008;51:435-443.[Abstract/Free Full Text]
- Iakoubova OA, Sabatine MS, Rowland CM, et al. Polymorphism in KIF6 gene and benefit from statins after acute coronary syndromes: results from the PROVE IT-TIMI 22 study J Am Coll Cardiol 2008;51:449-455.[Abstract/Free Full Text]
- Shiffman D, Chasman DI, Zee RYL, et al. A kinesin family member 6 variant is associated with coronary heart disease in the Women's Health study J Am Coll Cardiol 2008;51:444-448.[Abstract/Free Full Text]
- King JY, Ferrara R, Tabibiazar R, et al. Pathway analysis of coronary atherosclerosis Physiol Genomics 2005;23:103-118.[Abstract/Free Full Text]
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