BlueCross BlueShield of Tennessee Medical Policy Manual

KIF6 Genotyping for Predicting Cardiovascular Risk and/or Effectiveness of Statin Therapy

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.




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

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 (26 articles and/or guidelines reviewed) 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

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)




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