A common variant in the CDKN2B gene on chromosome 9p21 protects against coronary artery disease in Americans of African ancestry

Brian G. Kral, Rasika A. Mathias, Bhoom Suktitipat, Ingo Ruczinski, Dhananjay Vaidya, Lisa R. Yanek, Arshed A. Quyyumi, Riyaz S. Patel, A. Maziar Zafari, Viola Vaccarino, Elizabeth R. Hauser, William E. Kraus, Lewis C. Becker, Diane M. Becker

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


A 58kb region on chromosome 9p21.3 has consistently shown strong association with coronary artery disease (CAD) in multiple genome-wide association studies in populations of European and East Asian ancestry. In this study, we sought to further characterize the role of genetic variants in 9p21.3 in African American individuals. Apparently healthy African American siblings (n548) of patients with documented CAD <60 years of age were genotyped and followed for incident CAD for up to 17 years. Tests of association for 86 single-nucleotide polymorphisms (SNPs) across the 9p21.3 region in a generalized estimating equation logistic framework under an additive model adjusting for traditional risk factors, family, follow-up time and population stratification were performed. A single SNP within the CDKN2B gene met stringent criteria for statistical significance, including permutation-based evaluations. This variant, rs3217989, was common (minor allele (G) frequency 0.242), conveyed protection against CAD (odds ratio (OR)0.19, 95 confidence interval (CI): 0.07 to 0.50, P0.0008) and was replicated in a combined analysis of two additional casecontrol studies of prevalent CADMI in African Americans (n990, P0.024, OR0.779, 95 CI: 0.626-0.968). This is the first report of a CAD association signal in a population of African ancestry with a common variant within the CDKN2B gene, independent from previous findings in European and East Asian ancestry populations. The findings demonstrate a significant protective effect against incident CAD in African American siblings of persons with premature CAD, with replication in a combination of two additional African American cohorts.

Original languageEnglish (US)
Pages (from-to)224-229
Number of pages6
JournalJournal of Human Genetics
Issue number3
StatePublished - Mar 2011


  • 9p21
  • African American
  • CDKN2B
  • coronary artery disease
  • genetics

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'A common variant in the CDKN2B gene on chromosome 9p21 protects against coronary artery disease in Americans of African ancestry'. Together they form a unique fingerprint.

Cite this