Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018
Genetic testing to determine kinesin-like protein 6 (KIF6) Trp719Arg variant status is being evaluated to predict the risk of future cardiovascular events and predict response to statin therapy, particularly in high-risk individuals. The test detects a gene variant associated with increased coronary heart disease risk and classifies individuals as homozygous (normal risk) or heterozygous or homozygous carriers of Trp719Arg polymorphism for KIF6 (increased risk). Presence of a KIF6 variant is purported to predict response to statin therapy. The available version of the test is the Cardio IQ™ KIF6 Genotype.
KIF6 genotyping for predicting cardiovascular risk and/or the effectiveness of statin therapy is considered investigational.
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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. (7:2020). KIF6 genotyping for predicting cardiovascular risk and/or effectiveness of statin therapy (2.04.67). Retrieved July 23, 2020 from https://www.evidencepositioningsystem.com. (26 articles and/or guidelines reviewed)
CMS.gov: Centers for Medicare & Medicaid Services. Palmetto GBA. (2019, October). Local Coverage Article: MolDX: KIF6 genotype billing and coding guidelines (A53576). Retrieved July 23, 2020 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 individual 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)
ORIGINAL EFFECTIVE DATE: 10/8/2011
MOST RECENT REVIEW DATE: 7/8/2021
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