A common variant on chromosome 9p21 affects the risk of early-onset coronary artery disease

  • Zhong Chen
  • Qi Qian
  • Genshan MaEmail author
  • Jiahong Wang
  • Xiaoli Zhang
  • Yi Feng
  • Chengxing Shen
  • Yuyu Yao


Background Two single nucleotide polymorphisms (SNPs, rs10757278 and rs2383207) on chromosome 9p21 have been proved to be associated with myocardial infarction. We investigated whether these two genetic markers are determinants of early-onset coronary artery disease. Methods and results A total of 444 consecutive patients were studied including 212 cases with coronary stenosis 50% or previous myocardial infarction and 232 controls without documented coronary artery disease. Ligase detection reaction was performed to detect two SNPs. After adjustment of clinical parameters, significant associations were identified for the rs2383207 and rs10757278 SNPs, with A/G and G/G genetypes at rs10757278 and G/G genetype carriers at rs2383207 having a higher risk of early-onset coronary artery disease than carriers of A/A genotype (odds ratio [OR] 2.207, 95% CI: 1.069–4.394, = 0.028; OR 3.051, 95% CI: 1.086–8.567, = 0.004; OR 2.964, 95% CI: 1.063–8.265, = 0.038, respectively). There were no associations between rs10757278 and rs2383207 genotypes and the severity of coronary artery disease (both > 0.05). Conclusions The rs10757278 and rs2383207 variants are determinants for early-onset coronary artery disease. These markers may help the identification of patients at increased risk for early-onset coronary artery disease.


Coronary artery disease Early-onset Single nucleotide polymorphisms Genetic Gene 



Coronary artery disease


Confidence interval


Myocardial infarction


Odds ratio


Single nucleotide polymorphism



This study was supported by Nanjing Scientific Development Grant for 2006 (2006ZD016).


  1. 1.
    McPherson R, Pertsemlidis A, Kavaslar N et al (2007) A common allele on chromosome 9 associated with coronary heart disease. Science 316:1488–1491PubMedCrossRefGoogle Scholar
  2. 2.
    Helgadottir A, Thorleifsson G, Manolescu A et al (2007) A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science 316:1491–1493PubMedCrossRefGoogle Scholar
  3. 3.
    Shen GQ, Li L, Rao S et al (2008) Four SNPs on chromosome 9p21 in a South Korean population implicate a genetic locus that confers high cross-race risk for development of coronary artery disease. Arterioscler Thromb Vasc Biol 28:360–365. Epub 2007 Nov 29PubMedCrossRefGoogle Scholar
  4. 4.
    Jia EZ, Wang J, Yang ZJ et al (2007) Association of the mutation for the human carboxypetidase E gene exon 4 with the severity of coronary artery atherosclerosis. Mol Biol Rep 2007 Dec 16. Epub ahead of printGoogle Scholar
  5. 5.
    Zeng WW, Zhou B, Liu HR et al (2007) Identification of the tree shrew ATP-binding cassette transporter A1 (ABCA1) and its expression in tissues: cDNA sequence and expression of tree shrew ABCA1. Mol Biol Rep 2007 Dec 16. Epub ahead of printGoogle Scholar
  6. 6.
    Bazrgar M, Karimi M, Fathzadeh M et al (2007) Apolipoprotein E polymorphism in Southern Iran: E4 allele in the lowest reported amounts. Mol Biol Rep 2007 Jun 27. Epub ahead of printGoogle Scholar
  7. 7.
    Shah SH (2007) Gene polymorphisms and susceptibility to coronary artery disease. Pediatr Blood Cancer 48:738–741PubMedCrossRefGoogle Scholar
  8. 8.
    Christensen K, Murray JC (2007) What genome-wide association studies can do for medicine. N Engl J Med 356:1094–1097PubMedCrossRefGoogle Scholar
  9. 9.
    Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661–678CrossRefGoogle Scholar
  10. 10.
    Broeckel U, Hengstenberg C, Mayer B et al (2002) A comprehensive linkage analysis for myocardial infarction and its related risk factors. Nat Genet 30:210–214PubMedCrossRefGoogle Scholar
  11. 11.
    Fischer M, Broeckel U, Holmer S et al (2005) Distinct heritable patterns of angiographic coronary artery disease in families with myocardial infarction. Circulation 111:855–862PubMedCrossRefGoogle Scholar
  12. 12.
    Wichmann HE, Gieger C, Illig T (2005) KORA-gen—resource for population genetics, controls and a broad spectrum of disease phenotypes. Gesundheitswesen 67(Suppl 1):S26–S30PubMedCrossRefGoogle Scholar
  13. 13.
    Samani NJ, Erdmann J, Hall AS et al (2007) Genomewide association analysis of coronary artery disease. N Engl J Med 357:443–453PubMedCrossRefGoogle Scholar
  14. 14.
    Favis R, Day JP, Gerry NP (2000) Universal DNA array detection of small insertions and deletions in BRCA1 and BRCA2. Nat Biotechnol 18:561–564PubMedCrossRefGoogle Scholar
  15. 15.
    Xiao Z, Xiao J, Jiang Y et al (2006) A novel method based on ligase detection reaction for low abundant YIDD mutants detection in hepatitis B virus. Hepatol Res 34:150–155PubMedCrossRefGoogle Scholar
  16. 16.
    Lowe SW, Sherr CJ (2003) Tumor suppression by Ink4a-Arf: progress and puzzles. Curr Opin Genet Dev 13:77–83PubMedCrossRefGoogle Scholar
  17. 17.
    Hannon GJ, Beach D (1994) p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature 371:257–261PubMedCrossRefGoogle Scholar
  18. 18.
    Kalinina N, Agrotis A, Antropova Y et al (2004) Smad expression in human atherosclerotic lesions: evidence for impaired TGF-beta/Smad signaling in smooth muscle cells of fibrofatty lesions. Arterioscler Thromb Vasc Biol 24:1391–1396PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Zhong Chen
    • 1
  • Qi Qian
    • 1
  • Genshan Ma
    • 1
    Email author
  • Jiahong Wang
    • 1
  • Xiaoli Zhang
    • 1
  • Yi Feng
    • 1
  • Chengxing Shen
    • 1
  • Yuyu Yao
    • 1
  1. 1.Department of CardiologyThe Affiliated ZhongDa Hospital of Southeast UniversityNanjingPeople’s Republic of China

Personalised recommendations