Skip to main content
Log in

Cholesteryl ester transfer protein (CETP) −629C/A polymorphism and it,s effects on the serum lipid levels in metabolic syndrome patients

  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Metabolic syndrome is a relatively common disorder with significant morbidity worldwide. Cholesteryl ester transfer protein (CETP) plays a central role in the metabolism of lipoproteins. In this study the effect of −629C/A polymorphism on the concentration of CETP and plasma lipids pattern was elicited in metabolic syndrome patients and control subjects. For this, a sample of 200 patients diagnosed with metabolic syndrome disorder was studied in comparison with 200 healthy controls. This study was performed by using polymerase chain reaction and restriction fragment length polymorphisms. Genotype distribution and allelic frequencies were determined and compared in metabolic syndrome and healthy controls. To determine the relationship between −629C/A polymorphism and lipid levels, lipids and CETP concentration were measured in metabolic syndrome and normal subjects. The results showed a significant difference between two groups in terms of FBS, cholesterol, TG, HDL-C, LDL-C levels as well as BMI, waist circumference, systolic and diastolic blood pressure. The genotype frequencies for this polymorphism differed significantly between metabolic syndrome patients and controls (in control group: CC% 20.5, CA% 76, AA% 3.5 and in patient group: CC% 28.5, CA% 53.5, AA% 18) (p < 0.05) while there was no significant difference in the frequency of the alleles. In the two groups, the levels of the cholesteryl ester transfer protein in AA genotype were lower than other genotypes. In the control group, individuals with AA genotype had the highest levels of LDL-C and TC plasma concentration. Considering the results of this study, it can be concluded that the −629 AA genotype was associated with high cholesterol; high LDL-C and low CETP level, so that it can be related to metabolic syndrome.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Yamada Y, Kato K, Hibino T, Yokoi K, Matsuo H, Segawa T, Watanabe S, Ichihara S, Yoshida H, Satoh K, Nozawa Y (2007) Prediction of genetic risk for metabolic syndrome. Atherosclerosis 191(2):298–304

    Article  PubMed  CAS  Google Scholar 

  2. Agellon LB, Quinet EM, Gillette TG, Drayna DT, Brown ML, Tall AR (1990) Organization of the human cholesteryl ester transfer protein gene. Biochemistry 13 29(6):1372–1376

    Article  CAS  Google Scholar 

  3. Hassanzadeh T, Firoozrai M, Zonouz AE, Zavarehee A, Paoli M (2009) Taq1B polymorphism of cholesteryl ester transfer protein (CETP) gene in primary combined hyperlipidaemia. Indian J Med Res 129(3):293–298

    PubMed  CAS  Google Scholar 

  4. Weber O, Bischoff H, Schmeck C, Böttcher MF (2010) Cholesteryl ester transfer protein and its inhibition. Cell Mol Life Sci 67(18):3139–3149

    Article  PubMed  CAS  Google Scholar 

  5. Tall AR (1993) Plasma cholesteryl ester transfer protein. J Lipid Res 34(8):1255–1274

    PubMed  CAS  Google Scholar 

  6. Hassanzadeh T, Firoozrai M, Zonouz AE, Zavarehee A, Paoli M (2008) Association between cholesteryl ester transfer protein Taq1B polymorphism with lipid levels in primary hyperlipidemic patients. Eur J Lipid Sci Technol 110:225–231

    Article  Google Scholar 

  7. Ghasabeh TH, Firoozrai M, Zonouz AE, Radmehr H, Zavarehee A, Paoli M (2007) One common polymorphism of cholesteryl ester transfer protein gene in Iranian subjects with and without primary hypertriglyceridemia. Pak J Biol Sci 10(23):4224–4229

    Article  PubMed  CAS  Google Scholar 

  8. Wu JH, Lee YT, Hsu HC, Hsieh LL (2001) Influence of CETP gene variation on plasma lipid levels and coronary heart disease: a survey in Taiwan. Atherosclerosis 159(2):451–458

    Article  PubMed  CAS  Google Scholar 

  9. Dachet C, Poirier O, Cambien F, Chapman J, Rouis M (2000) New functional promoter polymorphism, CETP/−629, in cholesteryl ester transfer protein (CETP) gene related to CETP mass and high density lipoprotein cholesterol levels: role of Sp1/Sp3 in transcriptional regulation. Arterioscler Thromb Vasc Biol 20(2):507–515

    Article  PubMed  CAS  Google Scholar 

  10. Blankenberg S, Rupprecht HJ, Bickel C, Jiang XC, Poirier O, Lackner KJ, Meyer J, Cambien F, Tiret L (2003) Common genetic variation of the cholesteryl ester transfer protein gene strongly predicts future cardiovascular death in patients with coronary artery disease. J Am Coll Cardiol 41(11):1983–1989

    Article  PubMed  CAS  Google Scholar 

  11. Tai ES, Ordovas JM, Corella D, Deurenberg-Yap M, Chan E, Adiconis X, Chew SK, Loh LM, Tan CE (2003) The TaqIB and −629C>A polymorphisms at the cholesteryl ester transfer protein locus: associations with lipid levels in a multiethnic population. The 1998 Singapore National Health Survey. Clin Genet 63(1):19–30

    Article  PubMed  CAS  Google Scholar 

  12. Kuivenhoven JA, de Knijff P, Boer JM, Smalheer HA, Botma GJ, Seidell JC, Kastelein JJ, Pritchard PH (1997) Heterogeneity at the CETP gene locus. Influence on plasma CETP concentrations and HDL cholesterol levels. Arterioscler Thromb Vasc Biol 17(3):560–568

    Article  PubMed  CAS  Google Scholar 

  13. Rahimi Z, Nourozi-Rad R, Vaisi-Raygani A, Saidi MR, Rahimi Z, Ahmadi R, Yarani R, Hamzehee K, Parsian A (2011) Association between cholesteryl ester transfer protein TaqIB variants and risk of coronary artery disease and diabetes mellitus in the population of western Iran. Genet Test Mol Biomarkers. 15(11):813–819

    Article  PubMed  CAS  Google Scholar 

  14. Takata M, Inazu A, Katsuda S, Miwa K, Kawashiri MA, Nohara A, Higashikata T, Kobayashi J, Mabuchi H, Yamagishi M (2006) CETP (cholesteryl ester transfer protein) promoter −1337 C>T polymorphism protects against coronary atherosclerosis in Japanese patients with heterozygous familial hypercholesterolaemia. Clin Sci (Lond) 111(5):325–331

    Article  CAS  Google Scholar 

  15. Bernard S, Moulin P, Lagrost L, Picard S, Elchebly M, Ponsin G, Chapuis F, Berthezène F (1998) Association between plasma HDL-cholesterol concentration and Taq1B CETP gene polymorphism in non-insulin-dependent diabetes mellitus. J Lipid Res 39(1):59–65

    PubMed  CAS  Google Scholar 

  16. Lahdenperä S, Syvänne M, Kahri J, Taskinen MR (1996) Regulation of low-density lipoprotein particle size distribution in NIDDM and coronary disease: importance of serum triglycerides. Diabetologia 39:453–461

    Article  PubMed  Google Scholar 

  17. Ohtani R, Inazu A, Noji Y, Wakasugi T, Miwa K, Tada H, Kawashiri MA, Noguchi T, Nohara A, Kobayashi J, Koizumi J, Yamagishi M, Mabuchi H (2011) Novel mutations of cholesteryl ester transfer protein (CETP) gene in Japanese hyperalphalipoproteinemic subjects. Clin Chim Acta. doi:10.1016/j.cca.2011.11.010

    PubMed  Google Scholar 

  18. Sandhofer A, Kaser S, Ritsch A, Laimer M, Engl J, Paulweber B, Patsch JR, Ebenbichler CF (2006) Cholesteryl ester transfer protein in metabolic syndrome. Obesity (Silver Spring) 14(5):812–818

    Article  CAS  Google Scholar 

  19. Klerkx AH, Tanck MW, Kastelein JJ, Molhuizen HO, Jukema JW, Zwinderman AH, Kuivenhoven JA (2003) Haplotype analysis of the CETP gene: not TaqIB, but the closely linked −629C>A polymorphism and a novel promoter variant are independently associated with CETP concentration. Hum Mol Genet 12(2):111–123

    Article  PubMed  CAS  Google Scholar 

  20. Alberti KG, Zimmet PZ (1998) Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1 Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15(7):539–553

    Article  PubMed  CAS  Google Scholar 

  21. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (2001) Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel iii). JAMA 285(19):2486–2497

    Article  Google Scholar 

  22. Hegele RA, Pollex RL (2005) Genetic and physiological insights into the metabolic syndrome. Am J Physiol Regul Integr Comp Physiol 289(3):R663–R669

    Article  PubMed  CAS  Google Scholar 

  23. Sookoian S, Pirola CJ (2011) Metabolic syndrome: from the genetics to the pathophysiology. Curr Hypertens Rep 13(2):149–157

    Article  PubMed  CAS  Google Scholar 

  24. Padmaja N, Ravindra Kumar M, Soya SS, Adithan C (2007) Common variants of cholesteryl ester transfer protein gene and their association with lipid parameters in healthy volunteers of Tamilian population. Clin Chim Acta 375(1–2):140–146

    Article  PubMed  CAS  Google Scholar 

  25. Eiriksdottir G, Bolla MK, Thorsson B, Sigurdsson G, Humphries SE, Gudnason V (2001) The −629C>A polymorphism in the CETP gene does not explain the association of TaqIB polymorphism with risk and age of myocardial infarction in Icelandic men. Atherosclerosis 159(1):187–192

    Article  PubMed  CAS  Google Scholar 

  26. Thompson A, Di Angelantonio E, Sarwar N, Erqou S, Saleheen D, Dullaart RP, Keavney B, Ye Z, Danesh J (2008) Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk. JAMA 18 299(23):2777–2788

    Article  CAS  Google Scholar 

  27. Wang J, Ban MR, Zou GY, Cao H, Lin T, Kennedy BA, Anand S, Yusuf S, Huff MW, Pollex RL, Hegele RA (2008) Polygenic determinants of severe hypertriglyceridemia. Hum Mol Genet 17(18):2894–2899

    Article  PubMed  CAS  Google Scholar 

  28. Sandhofer A, Tatarczyk T, Laimer M, Ritsch A, Kaser S, Paulweber B, Ebenbichler CF, Patsch JR (2008) The Taq1B-variant in the cholesteryl ester-transfer protein gene and the risk of metabolic syndrome. Obesity (Silver Spring) 16(4):919–922

    Article  CAS  Google Scholar 

  29. Wilson PW (2008) CETP genes, metabolic effects, and coronary disease risk. JAMA 299(23):2795–2796

    Article  PubMed  CAS  Google Scholar 

  30. Yamada Y, Ichihara S, Kato K, Yoshida T, Yokoi K, Matsuo H, Watanabe S, Metoki N, Yoshida H, Satoh K, Aoyagi Y, Yasunaga A, Park H, Tanaka M, Lee W, Nozawa Y (2008) Genetic risk for metabolic syndrome: examination of candidate gene polymorphisms related to lipid metabolism in Japanese people. J Med Genet 45(1):22–28

    Article  PubMed  CAS  Google Scholar 

  31. Le Goff W, Guerin M, Petit L, Chapman MJ, Thillet J (2003) Regulation of human CETP gene expression: role of SP1 and SP3 transcription factors at promoter sites −690, −629, and −37. J Lipid Res 44(7):1322–1331

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

We are indebted to the Dey laboratory of Hamadan city for providing us with the samples. This study was financially supported by the Research Deputy of Hamadan University of Medical Sciences.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to T. Hassanzadeh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Akbarzadeh, M., Hassanzadeh, T., Saidijam, M. et al. Cholesteryl ester transfer protein (CETP) −629C/A polymorphism and it,s effects on the serum lipid levels in metabolic syndrome patients. Mol Biol Rep 39, 9529–9534 (2012). https://doi.org/10.1007/s11033-012-1817-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-012-1817-3

Keywords

Navigation