Kif6 Genotyping For Predicting Cardiovascular Risk

Genetic testing to determine kinesin-like protein 6 (KIF6) Trp719Arg variant status is being evaluated as a test to predict the risk of future cardiovascular events and as a test to predict response to statin therapy, particularly in high-risk patients. For individuals who are asymptomatic with risk of cardiovascular disease and undergoing treatment with statin therapy who receive testing for KIF6 Trp719Arg variant status, the evidence includes secondary analyses of randomized controlled trials, case-control studies, and a quasi-experimental single-arm study. Relevant outcomes are overall survival, test accuracy and validity, change in disease status, morbid events, and medication use. Data supporting the association between KIF6 variant status and coronary artery disease outcomes are contradictory. The most recent evidence from large populations with different vascular disease risk levels has not supported a significant association between coronary artery disease risk and the presence of the variant. Further, studies of the association between response to statin therapy and KIF6 variant status are mixed. However, a large meta-analysis has shown that carriers of the KIF6 variant derive greater clinical benefit from low-density lipoprotein cholesterol reduction (a 13% reduction in the risk of coronary artery disease outcomes) compared with noncarriers. Currently, no prospective randomized controlled trials have evaluated the impact of testing for KIF6 variants on changes in clinical management (eg, intensifying the statin treatment in carriers, use of alternative approaches for lipid management in noncarriers) or outcomes. One nonrandomized study has suggested that subjects with KIF6 genotype results showed greater adherence to statin therapy, but, overall, it is uncertain whether testing for KIF 6 variants will alter the clinical management decisions. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.