Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018
Genetic testing to determine the KIF6 Trp719Arg variant status is being evaluated as a prognostic test to predict risk of future cardiovascular events and as a pharmacogenetic test to predict response to statin therapy, particularly in high-risk individuals. The intent of testing for kinesin-like protein 6 (KIF6) gene variants in individuals receiving statin therapy for coronary artery disease (CAD) is to inform a decision as to whether an individual who has a variant is at a higher risk of a future cardiovascular event, and therefore statin treatment should be initiated or the existing statin dose should be increased.
Kinesin-like protein 6 (KIF6) belongs to the kinesin superfamily of proteins involved in intracellular transport. The exact function of the KIF6 gene is as yet undetermined.
KIF6 genotyping for predicting cardiovascular risk and/or the effectiveness of statin therapy is considered investigational.
Any specific products referenced in this policy are just examples and are intended for illustrative purposes only. It is not intended to be a recommendation of one product over another, and is not intended to represent a complete listing of all products available. These examples are contained in the parenthetical e.g. statement.
We develop Medical Policies to provide guidance to Members and Providers. This Medical Policy relates only to the services or supplies described in it. The existence of a Medical Policy is not an authorization, certification, explanation of benefits, or a contract for the service (or supply) that is referenced in the Medical Policy. For a determination of the benefits that a Member is entitled to receive under his or her health plan, the Member's health plan must be reviewed. If there is a conflict between the Medical Policy and a health plan, the express terms of the health plan will govern.
The literature that is currently available is limited and contradictory regarding outcomes. There is a lack of controlled studies in the published literature to evaluate the clinical importance of KIF6 genotyping to predict clinical events.
American College of Cardiology, American Heart Association. (2014). 2013 ACC/AHA guideline on the assessment of cardiovascular risk. Retrieved September 21, 2018 from https://www.acc.org/guidelines.
Angelini, S., Rosticci, M., Massimo, G., Musti, M., Ravegnini, G., Consolini, N., et al. (2017). Relationship between lipid phenotypes, overweight, lipid lowering drug response and KIF6 and HMG-CoA genotypes in a subset of the Brisighella heart study population. International Journal of Molecular Sciences, 19 (1), 49. Abstract retrieved September 21, 2018 from PubMed database.
BlueCross BlueShield Association. Evidence Positioning System. (6:2019). KIF6 genotyping for predicting cardiovascular risk and/or effectiveness of statin therapy (2.04.67). Retrieved September 30, 2019 from https://www.evidencepositioningsystem.com. (26 articles and/or guidelines reviewed)
CMS.gov: Centers for Medicare & Medicaid Services. Palmetto GBA. (2018, February). Local Coverage Article: MolDX: KIF6 genotype billing and coding guidelines (A53576). Retrieved September 21, 2018 from https://www.cms.gov.
Ference, B., Yoo, W., Flack, J., & Clarke, M. (2011). A common KIF6 polymorphism increases vulnerability to low-density lipoprotein cholesterol: two meta-analyses and a meta-regression analysis. PLoS One, 6 (12), e28834. (Level 2 evidence)
Hopewell, J., Parish, S., Clarke, R., Armitage, J., Bowman, L., Hager, J., et al. (2011). No impact of KIF 6 genotype on vascular risk and statin response among 18, 348 randomized patients in heart protection study. Journal of the American College of Cardiology, 57 (20), 2000-2007. (Level 1 Evidence)
Li, Y., Chen, Z., & Song. H. (2018). Association between KIF6 rs20455 polymorphism and the risk of coronary heart disease (CHD): a pooled analysis of 50 individuals studies including 40,059 cases and 64,032 controls. Lipids in Health and Disease, 17 (1), 4. (Level 1 evidence)
Peng, P., Lian, J., Huang, S., Xu, L., Huang, Y., Ba, Y., et al. (2012). Meta-analyses of KIF6 Trp719Arg in coronary heart disease and statin therapeutic effect. PLOS One, 7 (12). (Level 2 evidence)
Ruiz-Ramos, D., Hernández-Díaz, Y., Tovilla-Zárate, C., Juárez-Rojop, I., López-Narváez, M., González-Castro, T., et al. (2015). The Trp719Arg polymorphism of the KIF6 gene and coronary heart disease risk: systematic review and meta-analysis. BioMed Central, 153 (3). (Level 2 evidence)
Vishnuprabu, D., Geetha, S., Bhaskar, L., Mahapatra, N., & Munirajan, A. (2015). Genotyping and meta-analysis of KIFG Trp719Arg polymorphism in South Indian coronary artery disease patients: a case-control study. Meta Gene, 5, 129-134. (Level 3 evidence)
MOST RECENT REVIEW DATE: 11/14/2019
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