BlueCross BlueShield of Tennessee Medical Policy Manual

Genotyping for 9p21 Single Nucleotide Polymorphisms to Predict Risk of Cardiovascular Disease or Aneurysm

Does Not Apply to Commercial Genetic Testing Program effective 6/1/2018


A number of highly correlated single nucleotide polymorphisms (SNPs) found in the chromosome 9 region p21 locus (9p21) have been investigated for association with myocardial infarction (MI), particularly early onset MI, and other manifestations of cardiovascular disease. Associations with abdominal aortic aneurysm and intracranial aneurysm have also been reported. Genotyping for 9p21 SNPs has been investigated to identify individuals who may be at increased risk of cardiovascular disorders.




There is insufficient evidence to determine if the use of the 9p21 genetic variant predicts clinical events or improves health outcomes.


American College of Cardiology/American Heart Association. 2013 ACC/AHA guideline on the assessment of cardiovascular risk. Retrieved June 2, 2017 from

Chan, K., Patel, R., Newcombe, P., Nelson, C., Qasim, A., Epstein, S., et al. (2013). Association between the chromosome 9p21 locus and angiographic coronary artery disease burden: A collaborative meta-analysis. Journal of the American College of Cardiology, 61 (9), 957-970. (Level 1 evidence)

Dong, L., Wang, H., Wang, D., & Ding, H. (2013). Association of chromosome 9p21 genetic variants with risk of coronary heart disease in the East Asian population: a meta-analysis. Annuls of Human Genetics, 77, 183-190. (Level 1 evidence)

Matoo, S., Fallah, M., Daneshpour, M., Mousavi, R., Sedaghati, K., Hasanzad, M., & Azizi, F. (2017). Increased risk of CHD in the presence of rs7865618 (A allele): Tehran lipid and glucose study. Archives of Iranian Medicine, 20 (3), 153-157. Abstract retrieved June 2, 2017 from PubMed database.

Palmetto Government Benefits Administrators. (2019, October). Local Coverage Article: MolDX: 9p21 genotype test coding and billing guideline (A53657). Retrieved April 16, 2020 from

Patel, R., Schmidt, A., Tragante, V., McCubrey, M.S., Holmes, M., Howe, L., et al. (2019). Association of chromosome 9p21 with subsequent coronary heart disease events. Circulation: Genomic & Precision Medicine, 12 (4), e002471. (Level 1 evidence)

Pott, J., Burkhardt, R., Beutner, F., Horn, K., Teren, A., Kirsten, H., et al. (2017). Genome-wide meta-analysis identifies novel loci of plaque burden in carotid artery. Atherosclerosis, 259, 32-40. Abstract retrieved May 29, 2018 from PubMed database.

Sun, J., & Sun, F. (2017). Analysis on the polymorphism of chromosome region 9p21 and the susceptibility of carotid plaque. European Neurology, 77 (1-2), 25-31. (Abstract retrieved May 30, 2019 from PubMed database)

Xu, L.B., Zhang, N.N., Li, B., Weng, J.Y., Li, X.Y., Lu, W.C., et al. (2020). Rs10757274 gene polymorphisms in coronary artery disease: A systematic review and a meta-analysis. Medicine, 99 (3), e18841. Abstract retrieved April 16, 2020 from PubMed database.




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