Skip to main content
SpringerLink
Log in

Association of two variants in the interleukin-6 receptor gene and premature coronary heart disease in a Chinese Han population

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Two novel single nucleotide polymorphisms (SNPs; rs7529229 and rs2228145) in the interleukin-6 receptor (IL6R) gene have recently been associated with coronary heart disease (CHD) in a European population. We sought to replicate this finding and to investigate associations of these two SNPs with the severity and clinical phenotypes of premature CHD in a Chinese Han population. A total of 418 patients were studied, including 187 cases with coronary stenosis ≥50 % or acute myocardial infarction (males < 55 years and females < 65 years) and 231 controls without documented CHD. A ligase detection reaction was performed to detect rs7529229 and rs2228145. There were no differences between the controls and premature CHD groups in the frequencies for the three genotypes and alleles of rs7529229 and rs2228145 (all P > 0.05), nor did they differ between the two groups when grouped by gender (all P > 0.05). There were also no associations between these two SNPs and the severity of coronary lesions or clinical phenotypes of premature CHD (all P > 0.05). Our results do not support an association between rs7529229 or rs2228145 with premature CHD in the Chinese Han population. Further studies are warranted to elucidate the role of these two SNPs in the development of atherosclerosis and CHD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. He J, Gu D, Wu X et al (2005) Major causes of death among men and women in China. N Engl J Med 353:1124–1134

    Article  PubMed  CAS  Google Scholar 

  2. Hansson GK (2005) Inflammation, atherosclerosis, and coronary artery disease. N Engl J Med 352:1685–1695

    Article  PubMed  CAS  Google Scholar 

  3. Harismendy O, Notani D, Song X et al (2011) 9p21 DNA variants associated with coronary artery disease impair interferon-γ signaling response. Nature 470:264–268

    Article  PubMed  CAS  Google Scholar 

  4. Schoester M, Heinrich PC, Graeve L (1994) Regulation of interleukin-6 receptor expression by interleukin-6 in human monocytes–a re-examination. FEBS Lett 345:131–134

    Article  PubMed  CAS  Google Scholar 

  5. Kopf M, Baumann H, Freer G et al (1994) Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature 368:339–342

    Article  PubMed  CAS  Google Scholar 

  6. Chu NF, Lin FH, Chin HC et al (2011) Association between interleukin-6 receptor gene variations and atherosclerotic lipid profiles among young adolescents in Taiwan. Lipids Health Dis 10:136

    Article  PubMed  CAS  Google Scholar 

  7. Yudkin JS, Kumari M, Humphries SE et al (2000) Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 148:209–214

    Article  PubMed  CAS  Google Scholar 

  8. Naka T, Nishimoto N, Kishimoto T (2002) The paradigm of IL-6: from basic science to medicine. Arthritis Res 4:S233–S242

    Article  PubMed  Google Scholar 

  9. Yamasaki K, Taga T, Hirata Y et al (1988) Cloning and expression of the human interleukin-6 (BSF-2/IFN beta 2) receptor. Science 241:825–828

    Article  PubMed  CAS  Google Scholar 

  10. Hibi M, Murakami M, Saito M et al (1990) Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell 63:1149–1157

    Article  PubMed  CAS  Google Scholar 

  11. Rose-John S, Waetzig GH, Scheller J et al (2007) The IL-6/sIL-6R complex as a novel target for therapeutic approaches. Expert Opin Ther Targets 11:613–624

    Article  PubMed  CAS  Google Scholar 

  12. Boulanger MJ, Chow DC, Brevnova EE et al (2003) Hexameric structure and assembly of the interleukin-6/IL-6 alpha-receptor/gp130 complex. Science 300:2101–2104

    Article  PubMed  CAS  Google Scholar 

  13. Ridker PM, Rifai N, Stampfer MJ et al (2000) Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation 101:1767–1772

    Article  PubMed  CAS  Google Scholar 

  14. Danesh J, Kaptoge S, Mann AG et al (2008) Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review. PLoS Med 5:e78

    Article  PubMed  Google Scholar 

  15. Sattar N, Murray HM, Welsh P et al (2009) Prospective study of pravastatin in the elderly at risk (PROSPER) study group. Are markers of inflammation more strongly associated with risk for fatal than for nonfatal vascular events? PLoS Med 6:e1000099

    Article  PubMed  Google Scholar 

  16. Kluck PM, Wiegant J, Jansen RP et al (1993) The human interleukin-6 receptor alpha chain gene is localized on chromosome 1 band q21. Hum Genet 90:542–544

    Article  PubMed  CAS  Google Scholar 

  17. Esteve E, Villuendas G, Mallolas J et al (2006) Polymorphisms in the interleukin-6 receptor gene are associated with body mass index and with characteristic of the metabolic syndrome. Clin Endocrinol (Oxf) 65:88–91

    Article  CAS  Google Scholar 

  18. Hamid YH, Urhammer SA, Jensen DP et al (2004) Variation in the interleukin-6 receptor gene associates with type 2 diabetes in Danish whites. Diabetes 53:3342–3345

    Article  PubMed  CAS  Google Scholar 

  19. Jiang CQ, Lam TH, Liu B et al (2010) Interleukin-6 receptor gene polymorphism modulates interleukin-6 levels and the metabolic syndrome: GBCS-CVD. Obesity (Silver Spring) 18:1969–1974

    Article  CAS  Google Scholar 

  20. The Interleukin-6 Receptor Mendelian Randomisation Analysis (IL6R MR) Consortium (2012) The interleukin-6 receptor as a target for prevention of coronary heart disease: a Mendelian randomisation analysis. Lancet 379:1214–1224

    Article  Google Scholar 

  21. IL6R Genetics Consortium Emerging Risk Factors Collaboration (2012) Interleukin-6 receptor pathways in coronary heart disease: a collaborative meta-analysis of 82 studies. Lancet 379:1205–1213

    Article  Google Scholar 

  22. Kareinen A, Viitanen L, Halonen P et al (2001) Cardiovascular risk factors associated with insulin resistance cluster in families with early-onset coronary artery disease. Arterioscler Thromb Vasc Biol 21:1346–1352

    Article  PubMed  CAS  Google Scholar 

  23. Gensini GG (1983) A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol 51:606

    Article  PubMed  CAS  Google Scholar 

  24. Graham I, Atar D, Borch-Johnsen K et al (2007) European guidelines on cardiovascular disease prevention in clinical practice: executive summary: Fourth Joint Task Force of the European Society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Eur Heart J 28:2375–2414

    Article  PubMed  Google Scholar 

  25. Elliott P, Chambers JC, Zhang W (2009) Genetic loci associated with C-reactive protein levels and risk of coronary heart disease. JAMA 302:37–48

    Article  PubMed  CAS  Google Scholar 

  26. Casas JP, Shah T, Cooper J (2006) Insight into the nature of the CRP-coronary event association using Mendelian randomization. Int J Epidemiol 35:922–931

    Article  PubMed  Google Scholar 

  27. Kivimäki M, Lawlor DA, Eklund C (2007) Mendelian randomization suggests no causal association between C-reactive protein and carotid intima-media thickness in the young Finns study. Arterioscler Thromb Vasc Biol 27:978–979

    Article  PubMed  Google Scholar 

  28. Kivimäki M, Lawlor DA, Smith GD (2008) Does high C-reactive protein concentration increase atherosclerosis? The Whitehall II Study. PLoS One 3:e3013

    Article  PubMed  Google Scholar 

  29. Chen Z, Qian Q, Ma G et al (2009) A common variant on chromosome 9p21 affects the risk of early-onset coronary artery disease. Mol Biol Rep 36:889–893

    Article  PubMed  CAS  Google Scholar 

  30. Chen Z, Ding Z, Ma G et al (2011) Sterol regulatory element-binding transcription factor (SREBF)-2, SREBF cleavage-activating protein (SCAP), and premature coronary artery disease in a Chinese population. Mol Biol Rep 38:2895–2901

    Article  PubMed  CAS  Google Scholar 

  31. Quyyumi AA (2006) Women and ischemic heart disease: pathophysiologic implications from the women’s ischemia syndrome evaluation (WISE) Study and future research steps. J Am Coll Cardiol 47:s66–s71

    Article  PubMed  Google Scholar 

  32. Claassen Mette, Kirsten C, Sybrandy et al (2012) Gender gap in acute coronary heart disease: myth or reality? World J Cardiol 4:36–47

    Article  PubMed  Google Scholar 

  33. Zhong C, Zhen D, Qi Q et al (2010) A lack of association between adiponectin polymorphisms and coronary artery disease in a Chinese population. Genet Mol Biol 33:428–433

    Article  PubMed  CAS  Google Scholar 

Download references

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

  1. Department of Cardiology, The Affiliated Zhongda Hospital and School of Medicine, Southeast University, No. 87 Dingjiaqiao, Nanjing, 210009, People’s Republic of China

    Zhong Chen, Chengchun Tang, Jiandong Ding, Yi Feng & Genshan Ma

  2. Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, People’s Republic of China

    Qi Qian

Authors
  1. Zhong Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Qi Qian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chengchun Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jiandong Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yi Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Genshan Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Zhong Chen.

Additional information

Zhong Chen and Qi Qian contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, Z., Qian, Q., Tang, C. et al. Association of two variants in the interleukin-6 receptor gene and premature coronary heart disease in a Chinese Han population. Mol Biol Rep 40, 1021–1026 (2013). https://doi.org/10.1007/s11033-012-2143-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-012-2143-5

Keywords

Search

Navigation