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CRP Gene polymorphism contributes genetic susceptibility to dyslipidemia in Han Chinese population

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Abstract

C-reactive protein (CRP), an inflammatory marker that statistically predicts future cardiovascular risk, has been reported to be associated with plasma lipid level changes. Whether CRP genetic variants affect lipid metabolism is of importance to investigate. A community-based study population including 2,731 adult subjects aged 18–62 years was used to evaluate the association of CRP gene with dyslipidemia and five tagging SNPs (tagSNPs) were genotyped. Multiple logistic regression was applied to further evaluate relationships between the SNPs and lipid metabolism abnormality and general linear model was applied to compare plasma lipid levels between genotypes. Association analyses indicated that recessive model of SNPs rs876537 and rs4285692 had significant association with elevated HDL after adjustment for covariates. Odds ratio (OR) of rs876537 were 0.60 for HDL > 1.54 versus 1.04–1.54 mmol/L (P = 0.011), as well as, ORs were 0.617 for HDL > 1.83 versus ≤1.35 mmol/L (P = 0.002) and 0.724 for HDL = 1.59–1.83 versus ≤1.35 mmol/L (P = 0.028) respectively. OR of rs4285692 was 0.634 for HDL > 1.83 versus ≤1.35 mmol/L (P = 0.027). Further stratification analysis found significant associations of rs10737175 with elevated HDL (>1.54 vs. 1.04–1.54 mmol/L, OR 0.629 and P = 0.027) and elevated TG (≥1.70 vs. <1.70 mmol/L, ORs of additive and dominant models were 0.628, 0.545 and P values were 0.006, 0.003 respectively) in female. rs4285692 was significantly associated with elevated LDL (≥3.37 vs. <3.37 mmol/L), ORs equaled to 1.532, 2.281 for additive model and recessive model and P values were 0.028, 0.024 respectively in male. Furthermore, quantitative trait analysis indicated the variation T to C of rs876537 significantly affect decreased plasma HDL level (P = 0.014). Our findings suggest that CRP genetic polymorphisms independently had positive association with the risk of HDL, LDL and TG elevating and further replication in other large population and biological function research would be warranted.

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References

  1. Wu Z, Yao C, Zhao D, Wu G, Wang W, Liu J, Zeng Z, Wu Y (2001) Sino-MONICA project: a collaborative study on trends and determinants in cardiovascular diseases in China, part I: morbidity and mortality monitoring. Circulation 103:462–468

    Article  PubMed  CAS  Google Scholar 

  2. Flank P, Wahman K, Levi R, Fahlstrom M (2012) Prevalence of risk factors for cardiovascular disease stratified by body mass index categories in patients with wheelchair-dependent paraplegia after spinal cord injury. J Rehabil Med 44:440–443

    Article  PubMed  Google Scholar 

  3. Pepys MB, Hirschfield GM (2003) C-reactive protein: a critical update. J Clin Invest 111:1805–1812

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  4. Ridker PM, Rifai N, Rose L, Buring JE, Cook NR (2002) Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. N Engl J Med 347:1557–1565

    Article  PubMed  CAS  Google Scholar 

  5. Nordestgaard BG, Zacho J (2009) Lipids, atherosclerosis and CVD risk: is CRP an innocent bystander? Nutr Metab Cardiovasc Dis 19:521–524

    Article  PubMed  CAS  Google Scholar 

  6. Jingjin C, Tigang H (2006) Study on CRP expression of macrophage cultured in vitro induced by oxided low-density lipoprotein. Tianjin Med J 34:408–410

    Google Scholar 

  7. Venugopal SK, Devaraj S, Jialal I (2005) Macrophage conditioned medium induces the expression of C-reactive protein in human aortic endothelial cells: potential for paracrine/autocrine effects. Am J Pathol 166:1265–1271

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  8. Ballou SP, Lozanski G (1992) Induction of inflammatory cytokine release from cultured human monocytes by C-reactive protein. Cytokine 4:361–368

    Article  PubMed  CAS  Google Scholar 

  9. Pasceri V, Willerson JT, Yeh ET (2000) Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 102:2165–2168

    Article  PubMed  CAS  Google Scholar 

  10. Singh U, Dasu MR, Yancey PG, Afify A, Devaraj S, Jialal I (2008) Human C-reactive protein promotes oxidized low density lipoprotein uptake and matrix metalloproteinase-9 release in Wistar rats. J Lipid Res 49:1015–1023

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  11. Tabuchi M, Inoue K, Usui-Kataoka H, Kobayashi K, Teramoto M, Takasugi K, Shikata K, Yamamura M, Ando K, Nishida K, Kasahara J, Kume N, Lopez LR, Mitsudo K, Nobuyoshi M, Yasuda T, Kita T, Makino H, Matsuura E (2007) The association of C-reactive protein with an oxidative metabolite of LDL and its implication in atherosclerosis. J Lipid Res 48:768–781

    Google Scholar 

  12. Nissen SE, Tuzcu EM, Schoenhagen P, Crowe T, Sasiela WJ, Tsai J, Orazem J, Magorien RD, O’Shaughnessy C, Ganz P (2005) Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med 352:29–38

    Article  PubMed  CAS  Google Scholar 

  13. Kinlay S (2007) Low-density lipoprotein-dependent and -independent effects of cholesterol-lowering therapies on C-reactive protein: a meta-analysis. J Am Coll Cardiol 49:2003–2009

    Article  PubMed  CAS  Google Scholar 

  14. Aronson D, Bartha P, Zinder O, Kerner A, Shitman E, Markiewicz W, Brook GJ, Levy Y (2004) Association between fasting glucose and C-reactive protein in middle-aged subjects. Diabet Med 21:39–44

    Article  PubMed  CAS  Google Scholar 

  15. Young D, Camhi S, Wu T, Hagberg J, Stefanick M (2013) Relationships among changes in C-reactive protein and cardiovascular disease risk factors with lifestyle interventions. Nutr Metab Cardiovasc Dis 23:857–863

    Google Scholar 

  16. Seo SM, Baek SH, Jeon HK, Kang SM, Kim DS, Kim WS, Kim HS, Rha SW, Park JS, Seong IW, Ahn YK, Yoon JH, Cha TJ (2013) Correlations between the level of high-sensitivity C-reactive protein and cardiovascular risk factors in korean adults with cardiovascular disease or diabetes mellitus: the CALLISTO study. J Atheroscler Thromb 20:616–622

    Google Scholar 

  17. Zhang X, Kuang J, Xin Y, Wang Q (2008) The affection of simvastatin to serum lipide, high sensitivity C-reactive protein in elderly type 2 diabetic patients. China Med Her 5:18–20

    Google Scholar 

  18. Ansell BJ, Watson KE, Weiss RE, Fonarow GC (2003) hsCRP and HDL effects of statins trial (CHEST): rapid effect of statin therapy on C-reactive protein and high-density lipoprotein levels A clinical investigation. Heart Dis 5:2–7

    Google Scholar 

  19. Yue-long J, Lian-ping H, Jin-feng C, Bin-bin W, Chong S, Ying-shui Y (2011) Association of polymorphism in CRP gene with metabolic syndrome. Chin J Clin Pharmacol Ther 16:1391–1396

    Google Scholar 

  20. Zhao Y, Wang H, Liu S, Zhao X, Chen Y, Yang Y, Wang W, Wu Y, Chen A, Tang J, Yao Y, Li Y, Chen J, Shen C, Yang S (2012) Association study of CRP gene polymorphism and hypertension in Han Chinese population. Gene 512:41–46

    Google Scholar 

  21. Ridker PM (2007) C-reactive protein and the prediction of cardiovascular events among those at intermediate risk: moving an inflammatory hypothesis toward consensus. J Am Coll Cardiol 49:2129–2138

    Article  PubMed  CAS  Google Scholar 

  22. Danesh J, Wheeler JG, Hirschfield GM, Eda S, Eiriksdottir G, Rumley A, Lowe GD, Pepys MB, Gudnason V (2004) C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 350:1387–1397

    Article  PubMed  CAS  Google Scholar 

  23. Elkind MS, Luna JM, Coffey CS, McClure LA, Liu KM, Spitalnik S, Paik MC, Roldan A, White C, Hart R, Benavente O (2010) The levels of inflammatory markers in the treatment of stroke study (LIMITS): inflammatory biomarkers as risk predictors after lacunar stroke. Int J Stroke 5:117–125

    Google Scholar 

  24. den Hertog HM, van Rossum JA, van der Worp HB, van Gemert HM, de Jonge R, Koudstaal PJ, Dippel DW (2009) C-reactive protein in the very early phase of acute ischemic stroke: association with poor outcome and death. J Neurol 256:2003–2008

    Article  CAS  Google Scholar 

  25. Song IU, Kim JS, Kim YI, Lee KS, Jeong DS, Chung SW (2009) Relationship between high-sensitivity C-reactive protein and clinical functional outcome after acute ischemic stroke in a Korean population. Cerebrovasc Dis 28:545–550

    Article  PubMed  CAS  Google Scholar 

  26. Welsh P, Barber M, Langhorne P, Rumley A, Lowe GD, Stott DJ (2009) Associations of inflammatory and haemostatic biomarkers with poor outcome in acute ischaemic stroke. Cerebrovasc Dis 27:247–253

    Article  PubMed  CAS  Google Scholar 

  27. Elliott P, Chambers JC, Zhang W, Clarke R, Hopewell JC, Peden JF, Erdmann J, Braund P, Engert JC, Bennett D, Coin L, Ashby D, Tzoulaki I, Brown IJ, Mt-Isa S, McCarthy MI, Peltonen L, Freimer NB, Farrall M, Ruokonen A, Hamsten A, Lim N, Froguel P, Waterworth DM, Vollenweider P, Waeber G, Jarvelin MR, Mooser V, Scott J, Hall AS, Schunkert H, Anand SS, Collins R, Samani NJ, Watkins H, Kooner JS (2009) Genetic loci associated with C-reactive protein levels and risk of coronary heart disease. JAMA 302:37–48

    Google Scholar 

  28. Kong M, Lee C (2013) Genetic associations with C-reactive protein level and white blood cell count in the KARE study. Int J Immunogenet 40:120–125

    Google Scholar 

  29. Naitza S, Porcu E, Steri M, Taub DD, Mulas A, Xiao X, Strait J, Dei M, Lai S, Busonero F, Maschio A, Usala G, Zoledziewska M, Sidore C, Zara I, Pitzalis M, Loi A, Virdis F, Piras R, Deidda F, Whalen MB, Crisponi L, Concas A, Podda C, Uzzau S, Scheet P, Longo DL, Lakatta E, Abecasis GR, Cao A, Schlessinger D, Uda M, Sanna S, Cucca F (2012) A genome-wide association scan on the levels of markers of inflammation in Sardinians reveals associations that underpin its complex regulation. PLoS Genet 8(1):e1002480

    Google Scholar 

  30. Chu AY, Guilianini F, Barratt BJ, Nyberg F, Chasman DI, Ridker PM (2012) Pharmacogenetic determinants of statin-induced reductions in C-reactive protein. Circ Cardiovasc Genet 5:58–65

    Article  PubMed  CAS  Google Scholar 

  31. Perry TE, Muehlschlegel JD, Liu KY, Fox AA, Collard CD, Body SC, Shernan SK (2009) C-Reactive protein gene variants are associated with postoperative C-reactive protein levels after coronary artery bypass surgery. BMC Med Genet 10:38

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  32. Melzer D, Perry JR, Hernandez D, Corsi AM, Stevens K, Rafferty I, Lauretani F, Murray A, Gibbs JR, Paolisso G, Rafiq S, Simon-Sanchez J, Lango H, Scholz S, Weedon MN, Arepalli S, Rice N, Washecka N, Hurst A, Britton A, Henley W, van de Leemput J, Li R, Newman AB, Tranah G, Harris T, Panicker V, Dayan C, Bennett A, McCarthy MI, Ruokonen A, Jarvelin MR, Guralnik J, Bandinelli S, Frayling TM, Singleton A, Ferrucci L (2008) A genome-wide association study identifies protein quantitative trait loci (pQTLs). PLoS Genet 4:e1000072

  33. Morita A, Nakayama T, Doba N, Hinohara S, Soma M (2006) Polymorphism of the C-reactive protein (CRP) gene is related to serum CRP Level and arterial pulse wave velocity in healthy elderly Japanese. Hypertens Res 29:323–331

    Article  PubMed  CAS  Google Scholar 

  34. Crawford DC, Sanders CL, Qin X, Smith JD, Shephard C, Wong M, Witrak L, Rieder MJ, Nickerson DA (2006) Genetic variation is associated with C-reactive protein levels in the Third National Health and Nutrition Examination Survey. Circulation 114:2458–2465

    Article  PubMed  CAS  Google Scholar 

  35. Yan M, Zhao L, Zheng F, Sun X, Zhang Y, Wang C (2007) The relationship between gene polymorphism and CRP level in a Chinese Han population. Biochem Genet 45:1–9

    Article  PubMed  CAS  Google Scholar 

  36. Shen C, Sun X, Wang H, Wang B, Xue Y, Li Y, Chen J, Jiang Y (2013) Association study of CRP gene and ischemic stroke in a Chinese Han Population. J Mol Neurosci 49:559–566

    Google Scholar 

  37. den Hertog HM, van den Herik EG, Dippel DW, Koudstaal PJ, de Maat MP (2010) Variation in the C-reactive protein gene is associated with serum levels of CRP in patients with acute ischemic stroke. Cerebrovasc Dis 29:372–375

    Article  CAS  Google Scholar 

  38. Ben Assayag E, Shenhar-Tsarfaty S, Bova I, Berliner S, Usher S, Peretz H, Shapira I, Bornstein NM (2009) Association of the −757T > C polymorphism in the CRP gene with circulating C-reactive protein levels and carotid atherosclerosis. Thromb Res 124:458–462

    Google Scholar 

  39. Pasalic D, Marinkovic N, Grskovic B, Ferencak G, Bernat R, Stavljenic-Rukavina A (2009) C-reactive protein gene polymorphisms affect plasma CRP and homocysteine concentrations in subjects with and without angiographically confirmed coronary artery disease. Mol Biol Rep 36:775–780

    Article  PubMed  CAS  Google Scholar 

  40. Shih PB, Manzi S, Shaw P, Kenney M, Kao AH, Bontempo F, Barmada MM, Kammerer C, Kamboh MI (2008) Genetic variation in C-reactive protein (CRP) gene may be associated with risk of systemic lupus erythematosus and CRP concentrations. J Rheumatol 35:2171–2178

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  41. Yu BL, Wu CL, Zhao SP (2012) Plasma apolipoprotein O level increased in the patients with acute coronary syndrome. J Lipid Res 53:1952–1957

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  42. Maingrette F, Li L, Renier G (2008) C-reactive protein enhances macrophage lipoprotein lipase expression. J Lipid Res 49:1926–1935

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 81273165, No. 81072367, No. 81102180 and No. 30800947), the Natural Science Foundation of Jiangsu Province (No. BK2011776) Science & Technology Program of Jiangsu Province (No. BE2009681), Key Science & Technology Program of Jiangsu Province (No. BE2009613) and the Priority Academic Program for the Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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The authors have no conflicts of interest to declare.

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Authors and Affiliations

  1. Department of Cardiology, The Fourth People’s Hospital of Shenzhen City, Affiliated to Guangdong Medical College, Shenzhen City, 518033, China

    Wenbin Wei

  2. Department of Cardiology, Affiliated Yixing People’s Hospital of Jiangsu University, People’s Hospital of Yixing City, Yixing, 214200, China

    Song Yang, Xianghai Zhao, Yanchun Chen & Wen Wang

  3. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, 211166, China

    Yingru Qiu, Hairu Wang, Sijun Liu, Jinfeng Chen, Hongbing Shen & Chong Shen

  4. Nanjing Institute of Industry Technology, Nanjing, 210046, China

    Hairu Wang

  5. Department of Neurology, Affiliated Yixing People’s Hospital of Jiangsu University, People’s Hospital of Yixing City, Yixing, 214200, China

    Yanping Zhao

  6. School of Public Health, Hebei United University, Tangshan, 063000, China

    Yun Li

  7. Division of Chronic Disease Control, Center for Disease Control of Jiangsu Province, Nanjing, 210009, Jiangsu, China

    Ming Wu

  8. Division of Chronic Disease Control and Community Health, Chinese Center for Disease Control and Prevention, Beijing, China

    Xiaoming Shi

  9. Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232-6300, USA

    Wenbin Wei, David Zhao & Yanru Su

  10. Department of Preventive Medicine, Wannan Medical College, Wuhu, 241001, China

    Ying-shui Yao

  11. Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, No. 140 Hanzhong Road, Nanjing, 210029, China

    Chong Shen

  12. Department of Preventive Medicine, Wannan Medical College, No. 22, Wen Chang Road Wuhu, Anhui, 241002, China

    Ying-shui Yao

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  1. Wenbin Wei
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  2. Song Yang
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  4. Hairu Wang
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  10. Wen Wang
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  15. David Zhao
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  18. Ying-shui Yao
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Corresponding authors

Correspondence to Chong Shen or Ying-shui Yao.

Additional information

Wenbin Wei, Song Yang and Yingru Qiu equally contributed to this work.

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Wei, W., Yang, S., Qiu, Y. et al. CRP Gene polymorphism contributes genetic susceptibility to dyslipidemia in Han Chinese population. Mol Biol Rep 41, 2335–2343 (2014). https://doi.org/10.1007/s11033-014-3087-8

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