Advertisement

Journal of Molecular Medicine

, Volume 83, Issue 1, pp 72–78 | Cite as

−717A>G polymorphism of human C-reactive protein gene associated with coronary heart disease in ethnic Han Chinese: the Beijing atherosclerosis study

  • Jianhong Chen
  • Jiangong Zhao
  • Jianfeng Huang
  • Shaoyong Su
  • Boqin Qiang
  • Dongfeng Gu
Original Article

Abstract

Serum C-reactive protein (CRP) has been strongly implicated in the pathogenesis of coronary heart disease (CHD). We report here on the association between gene coding for CRP and CHD in the ethnic Han population of China. For this purpose two polymorphisms of −717A>G and +2147A>G of the CRP gene were identified by direct sequencing of genomic DNA derived from 48 randomly selected patients and these were further investigated for associations with CHD in 619 male patients and 615 age-matched male normal controls. The frequency of A allele carriers of −717A>G polymorphism was significantly higher in patients than in controls by univariate analysis. After controlling for other risk factors the association between this polymorphism and CHD remained significant by multivariate logistic regression analysis. Individuals carrying the −717A allele had an approx. 6.8-fold higher risk of developing CHD (odds ratio 6.84 compared with those not carrying this allele). Haplotype analysis confirmed the results of individual polymorphism analyses. However, the resolution of effect size is poor, which may be due to the deficiency in sample size of this study. Neither polymorphism was observed to have an influence on serum CRP level. Since the frequency difference between CHD cases and controls for the −717A allele carriers is only 2.28%, and homozygosity for −717G occurs in only 1.78% of subjects, −717 A>G polymorphism is not a major determinant of population genetic risk of CHD in the Chinese population. The association of this polymorphism with CHD supports the belief that carriers of −717A allele of the CRP gene are genetically predisposed to CHD in the Chinese Han population, and it remains possible that this polymorphism is in disequilibrium with one as yet unidentified functional polymorphism in the vicinity.

Keywords

Coronary disease Genetics C-reactive protein Inflammatory reaction Single nucleotide polymorphism 

Abbreviations

BMI

Body mass index

CHD

Coronary heart disease

CRP

C-reactive protein

HDL

High-density lipoprotein

LDL

Low-density lipoprotein

SNP

Single-nucleotide polymorphism

Notes

Acknowledgements

This work was funded by grants 2002BA711A05, 2002BA711A08, and 2002BA711A10 of the National Tenth Five-Year Plan Key Programs from Ministry of Science and Technology of the People’s Republic of China and H020220030130 Biomedical Project from the Council of Science and Technology, Beijing.

References

  1. 1.
    Taubes G (2002) Does inflammation cut to the heart of the matter? Science 296:242–245CrossRefPubMedGoogle Scholar
  2. 2.
    Ross R (1999) Atherosclerosis: an inflammatory disease. N Engl J Med 340:115–126CrossRefPubMedGoogle Scholar
  3. 3.
    Libby P (1995) Molecular bases of the acute coronary syndromes. Circulation 91:2844–2850PubMedGoogle Scholar
  4. 4.
    Libby P, Ridker PM (1999) Novel inflammatory markers of coronary risk: theory versus practice. Circulation 100:1148–1150PubMedGoogle Scholar
  5. 5.
    Rader DJ (2000) Inflammatory markers of coronary risk. N Engl J Med 343:1179–1182CrossRefPubMedGoogle Scholar
  6. 6.
    Lindahl B, Toss H, Siegbahn A, Venge P, Wallentin L (2000) Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary disease. N Engl J Med 343:1139–1147CrossRefPubMedGoogle Scholar
  7. 7.
    Liuzzo G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, Maseri A (1994) The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina. N Engl J Med 331:417–424CrossRefPubMedGoogle Scholar
  8. 8.
    Biasucci LM, Liuzzo G, Grillo RL, Caligiuri G, Rebuzzi AG, Buffon A, Summaria F, Ginnetti F, Fadda G, Maseri A (1999) Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability. Circulation 99:855–860PubMedGoogle Scholar
  9. 9.
    Ferreiros ER, Boissonnet CP, Pizarro R, Merletti PF, Corrado G, Cagide A, Bazzino OO (1999) Independent prognostic value of elevated C-reactive protein in unstable angina. Circulation 100:1958–1963PubMedGoogle Scholar
  10. 10.
    Hak AE, Stehouwer CD, Bots ML, Polderman KH, Schalkwijk CG, Westendorp IC, Hofman A, Witteman JC (1999) Association of C-reactive protein with measures of obesity, insulin resistance, and subclinical atherosclerosis in healthy, middle-aged women. Arterioscler Thromb Vasc Biol 19:1986–1991PubMedGoogle Scholar
  11. 11.
    Visser M, Bouter LM, Mcquitlan GM, Wener MH, Harris TB (1999) Elevated C-reactive protein levels in overweight and obese adults. JAMA 282:2131–2135CrossRefPubMedGoogle Scholar
  12. 12.
    Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW (1999) C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 19:972–978PubMedGoogle Scholar
  13. 13.
    Du Clos TW (2000) Function of C-reactive protein. Ann Med 32:274–278PubMedGoogle Scholar
  14. 14.
    Klein TC, Doffinger R, Pepys MB, Ruther U, Kyewski B (1995) Tolerance and immunity to the inducible self-antigen C-reactive protein in transgenic mice. Eur J Immunol 25:3489–3495PubMedGoogle Scholar
  15. 15.
    Zee RY, Ridker PM (2002) Polymorphism in the human C-reactive protein (CRP) gene, plasma concentrations of CRP, and the risk of future arterial thrombosis. Atherosclerosis 162:217–219CrossRefPubMedGoogle Scholar
  16. 16.
    Cao H, Hegele RA (2000) Human C-reactive protein (CRP) 1059G/C polymorphism. J Hum Genet 45:100–101CrossRefPubMedGoogle Scholar
  17. 17.
    Xiaoling Wang, Zhongjie Fan, Jianfeng Huang, Shaoyong Su, Quanjun Yu, Jiangong Zhao, Rutai Hui, Zhijian Yao, Yan Shen, Boqin Qiang, Dongfeng Gu (2003) Extensive association analysis between polymorphisms of PON gene cluster with coronary heart disease in Chinese Han population. Arterioscler Thromb Vasc Biol 23:328–334CrossRefPubMedGoogle Scholar
  18. 18.
    Rose GA, Blackburn H (1968) Cardiovascular survey methods, no56, 1st edn. World Health Organization, GenevaGoogle Scholar
  19. 19.
    Ridker PM, Buring JE, Shih J, Matias M, Hennekens CH (1998) Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. Circulation 98:731–733PubMedGoogle Scholar
  20. 20.
    Joseph S, David WR (2001) Isolation of high-molecular-weight DNA from mammalian cells using proteinase K and phenol. In: Joseph S, David WR (eds) Molecular cloning: a laboratory manual, 3rd edn. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 6.4–6.11Google Scholar
  21. 21.
    Schaid DJ, Rowland CM, Tines DE, Jacobson RM, Poland GA (2002) Score tests for association between traits and haplotypes when linkage phase Is ambiguous. Am J Hum Genet 70:425–434CrossRefPubMedGoogle Scholar
  22. 22.
    Ridker PM, Hennekens CH, Buring JE, Rifai N (2000) C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 342:836–843CrossRefPubMedGoogle Scholar
  23. 23.
    Brull DJ, Norma Serrano, F Zito, Lisa Jones, Montgomery HE Rumley A, Sharma P, Lowe GDO, World MJ, Humphries SE, Hingorani AD (2003) Human CRP gene polymorphism influences CRP levels—implications for the prediction and pathogenesis of coronary heart disease. Arterioscler Thromb Vasc Biol 23:2063–2069CrossRefPubMedGoogle Scholar
  24. 24.
    Pankow JS, Folsom AR, Cushman M, Borecki IB, Hopkins PN, Eckfeldt JH, Tracy PP (2001) Familial and genetic determinants of systemic markers of inflammation: the NHLBI family heart study. Atherosclerosis 154:681–689CrossRefPubMedGoogle Scholar
  25. 25.
    Risch NJ (2000) Searching for genetic determinants in the new millennium. Nature 405:847–856CrossRefPubMedGoogle Scholar
  26. 26.
    Libby P, Ridker PM, Maseri A (2002) Inflammation and atherosclerosis. Circulation 105:1135–1143CrossRefPubMedGoogle Scholar
  27. 27.
    Hoehe MR, Köpke K, Wendel B, Rohde K, Flachmeier C, Kidd KK, Berrettini WH, Church GM (2000) Sequence variability and candidate gene analysis in complex disease: association of opioid receptor gene variation with substance dependence. Hum Mol Genet 9:2895–2908CrossRefPubMedGoogle Scholar
  28. 28.
    Aldons JL (2000) Atherosclerosis. Nature 407:233–241CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Jianhong Chen
    • 1
    • 2
  • Jiangong Zhao
    • 1
  • Jianfeng Huang
    • 1
  • Shaoyong Su
    • 1
  • Boqin Qiang
    • 2
  • Dongfeng Gu
    • 1
    • 2
  1. 1.Division of Population Genetics and Prevention, Fu Wai HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
  2. 2.National Human Genome Center at BeijingBeijingChina

Personalised recommendations