A genetic marker peddled as a predictor of coronary artery disease actually has no significant bearing on the matter, according to a recently published Stanford-led study.
The study was led by Thomas Quertermous, professor in cardiovascular medicine, and Themistocles Assimes, assistant professor of medicine, in collaboration with more than 130 coauthors throughout Europe and North America.
Published online in the “Journal of the American College of Cardiology” on Oct. 8, the study dispels the claim that a KIF6 gene polymorphism is associated with an increased risk for coronary artery disease. Coronary artery disease, a disease of cholesterol buildup in the arteries of the heart that often results in fatal heart attacks, is the number one killer in the United States.
The collaborators used a meta-analysis of genome-wide association studies to assess the effects of KIF6 polymorphisms on more than 17,000 individuals with coronary artery disease and more than 40,000 individuals without the disease. As opposed to some previous studies with small subject pools that cited a 22 to 55 percent greater risk of disease for those with the KIF6 variant, this study found no significant increased risk.
The mistaken risk association between the KIF6 gene and coronary artery disease gained momentum with a minority of the medical community when medical devices company CELERA Diagnostics made and marketed a test kit for doctors to take patients’ samples, Quertermous said.
Both positive and negative studies existed prior to CELERA marketing its test kits.
“It was a murky feeling to begin with,” Assimes said in reference to the mistaken gene-disease association. This murky feeling amid the gaining momentum of the CELERA test kits prompted the study.
This mistake is common to complex human diseases, such as coronary artery disease, that have complex genetics (that is, multiple small defects each with small effects) and gene-environment interactions, as opposed to “Mendelian” genetic diseases, where a single gene defect causes a large effect.
Currently, 13 valid molecular markers for coronary artery disease have been identified using genome-wide association studies. However, more markers are necessary for this technology to be truly useful in clinical practice, Assimes said. “We need to reach a threshold.”
Researchers hope to identify new genes to identify drug targets and develop new drugs for those pathways, said Joshua Knowles, who runs the clinic of inherited coronary diseases at Stanford’s Center of Inherited Cardiovascular Disease.
“For people with cardiovascular disease, the first symptom is usually death,” Quertermous said. “We want to intervene.”
The field of genetic markers as predictors of complex human diseases is still in its infancy, Knowles said.
Most genetic variants thus far are not widely used as a diagnosis tool in a clinical setting and more trials are needed.
Doctors are not yet paying much attention to genetic markers for complex human diseases, Quertermous said. Nonetheless, Assimes predicts that ten years from now, genetic markers will be an important assessment tool for physicians.
However, using markers will require medical schools and physicians to brush up on genetics, which is “understudied and under-taught at most medical schools,” Knowles said.
Because this technology is still maturing, insurance companies have given it little attention as well. When the insurance companies do take note, patients will be partially protected by the Genetic Information Nondiscrimination Act of 2008, which prohibits discrimination based on genetics for life — but not health — insurance, Knowles said, putting even more pressure on geneticists to catch these mistakes such as this one well beforehand.