Biochemical Genetics

, Volume 53, Issue 7–8, pp 184–199 | Cite as

Studies of the CETP TaqIB and ApoE Polymorphisms in Southern Thai Subjects with the Metabolic Syndrome

  • Nutjaree JeenduangEmail author
  • Sureerut Porntadavity
  • Manit Nuinoon
  • Dararat Horpet
  • Nongyao Thepkwan
  • Pattamawadee Thaworn
  • Suporn Theanmontri
Original Article


Several genetic factors have been investigated responsible for metabolic syndrome (MetS). The aim of this study was to investigate the association between cholesteryl ester transfer protein (CETP) TaqIB and apolipoprotein E (ApoE) polymorphisms and MetS in 378 subjects from Southern Thailand. Subjects were divided into MetS+ (n = 121) and MetS− (n = 257) groups according to the criteria of National Cholesterol Education Program Adult Treatment Panel III (NCEP ATPIII). The CETP TaqIB and ApoE polymorphisms were analyzed by polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) technique. Logistic regression analysis revealed no association of CETP TaqIB and ApoE variants with MetS, after adjustment for age and sex. However, ε4 allele had a significantly increased odds ratio (OR) of reduced high-density lipoprotein–cholesterol (HDL-C) levels when compared with ε3 allele (OR 1.91; 95 % CI 1.11–3.29, p = 0.020). This suggests that CETP TaqIB and ApoE polymorphisms may not be considered as genetic risk factors for MetS in a Southern Thai population. However, ε4 allele which is associated with one metabolic component, low HDL-C levels, might predispose the subjects to develop metabolic disturbances.


ApoE CETP TaqIB Metabolic syndrome Polymorphism 



We would like to thank all the study participants for their cooperation. This work was supported by a Young Research Grant No. WU55305, financed by Institute of Research and Development, Walailak University.

Conflict of interest

The authors declare that there are no conflicts of interest.


  1. Aekplakorn W, Kessomboon P, Sangthong R, Chariyalertsak S, Putwatana P, Inthawong R, Nitiyanant W, Taneepanichskul S, NHES IV study group (2011) Urban and rural variation in clustering of metabolic syndrome components in the Thai population: results from the fourth National Health Examination Survey 2009. BMC Public Health 11:854. doi: 10.1186/1471-2458-11-854 PubMedCentralPubMedCrossRefGoogle 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 29:1372–1376PubMedCrossRefGoogle Scholar
  3. Arai T, Yamashita S, Hirano K et al (1994) Increased plasma cholesteryl ester transfer protein in obese subjects. A possible mechanism for the reduction of serum HDL cholesterol levels in obesity. Arterioscler Thromb 14:1129–1136PubMedCrossRefGoogle Scholar
  4. Bennet AM, Di Angelantonio E, Ye Z, Wensley F, Dahlin A, Ahlbom A, Keavney B, Collins R, Wiman B, de Faire U, Danesh J (2007) Association of apolipoprotein E genotypes with lipid levels and coronary risk. JAMA 298:1300–1311PubMedCrossRefGoogle Scholar
  5. Chaudhary R, Likidlilid A, Peerapatdit T, Tresukosol D, Srisuma S, Ratanamaneechat S, Sriratanasathavorn C (2012) Apolipoprotein E gene polymorphism: effects on plasma lipids and risk of type 2 diabetes and coronary artery disease. Cardiovasc Diabetol 11:36. doi: 10.1186/1475-2840-11-36 PubMedCentralPubMedCrossRefGoogle Scholar
  6. Chuenta W, Phonrat B, Tungtrongchitr A, Limwongse C, Chongviriyaphan N, Santiprabhob J, Tungtrongchitr R (2015) Common variations in the FTO gene and obesity in Thais: a family-based study. Gene 558(1):75–81PubMedCrossRefGoogle Scholar
  7. 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 20:507–515PubMedCrossRefGoogle Scholar
  8. Dallongeville J, Lussier-Cacan S, Davignon J (1992) Modulation of plasma triglyceride levels by apoE phenotype: a meta-analysis. J Lipid Res 33:447–454PubMedGoogle Scholar
  9. Drayna D, Lawn R (1987) Multiple RFLPs at the human cholesteryl ester transfer protein (CETP) locus. Nucleic Acids Res 15:4698PubMedCentralPubMedCrossRefGoogle Scholar
  10. Dullaart RP, Sluiter WJ, Dikkeschei LD, Hoogenberg K, Van Tol A (1994) Effect of adiposity on plasma lipid transfer protein activities: a possible link between insulin resistance and high density lipoprotein metabolism. Eur J Clin Invest 24:188–194PubMedCrossRefGoogle Scholar
  11. Elsammak MY, Al-Sharkaweey RM, Fahmy M, Reda AA, Farid W, Emara A, Hassan H, Kandil MH (2011) Taq 1B polymorphism of cholesteryl ester transfer protein (CETP) in Egyptian patients with metabolic syndrome. Diabetes Metab Syndr 5(2):61–65PubMedCrossRefGoogle Scholar
  12. Ferreira DC, Costa TF, Aguiar SFL, Marques AR, Ramos SA, Gomes KB, Alvarez-Leite JI (2011) Association of Apoliprotein E polymorphisms and metabolic syndrome in subjects with extreme obesity. Clin Chim Acta 412:1559–1562PubMedCrossRefGoogle Scholar
  13. Fidani L, Goulas A, Crook R, Petersen RC, Tangalos E, Kotsis A, Hardy J (2004) An association study of the cholesteryl ester transfer protein TaqI B polymorphism with late onset alzheimer’s disease. Neurosci Lett 357:152–154PubMedCrossRefGoogle Scholar
  14. Freeman DJ, Griffin BA, Holmes AP, Lindsay GM, Gaffney D, Packard CJ, Shepherd J (1994) Regulation of plasma HDL cholesterol and subfraction distribution by genetic and environmental factors. Associations between the TaqI B RFLP in the CETP gene and smoking and obesity. Arterioscler Thromb 14:336–344PubMedCrossRefGoogle Scholar
  15. Grundy SM, Cleeman JI, Daniels SR et al (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation 112:2735–2752PubMedCrossRefGoogle Scholar
  16. Gustavsson J, Mehlig K, Leander K, Strandhagen E, Björck L, Thelle DS, Lissner L, Blennow K, Zetterberg H, Nyberg F (2012) Interaction of apolipoprotein E genotype with smoking and physical inactivity on coronary heart disease risk in men and women. Atherosclerosis 220:486–492PubMedCrossRefGoogle Scholar
  17. Hannuksela ML, Liinamaa MJ, Kesaniemi YA, Savolainen MJ (1994) Relation of polymorphisms in the cholesteryl ester transfer protein gene to transfer protein activity and plasma lipoprotein levels in alcohol drinkers. Atherosclerosis 110:35–44PubMedCrossRefGoogle Scholar
  18. Hayashibe H, Asayama K, Nakane T, Uchida N, Kawada Y, Nakazawa S (1997) Increased plasma cholesteryl ester transfer activity in obese children. Atherosclerosis 129:53–58PubMedCrossRefGoogle Scholar
  19. Kataoka S, Robbins DC, Cowan LD, Go O, Yeh JL, Devereux RB, Fabsitz RR, Lee ET, Welty TK, Howard BV (1996) Apolipoprotein E polymorphism in American Indians and its relation to plasma lipoproteins and diabetes. The Strong Heart Study. Arterioscler Thromb Vasc Biol 16:918–925PubMedCrossRefGoogle Scholar
  20. Kauma H, Savolainen MJ, Heikkilä R, Rantala AO, Lilja M, Reunanen A, Kesäniemi YA (1996) Sex difference in the regulation of plasma high density lipoprotein cholesterol by genetic and environmental factors. Hum Genet 97:156–162PubMedCrossRefGoogle Scholar
  21. Kawasaki I, Tahara H, Emoto M, Shoji T, Nishizawa Y (2002) Relationship between TaqIB cholesteryl ester transfer protein gene polymorphism and macrovascular complications in Japanese patients with type 2 diabetes. Diabetes 51(3):871–874PubMedCrossRefGoogle Scholar
  22. Kessling A, Ouellette S, Bouffard O, Chamberland A, Bétard C, Selinger E, Xhignesse M, Lussier-Cacan S, Davignon J (1992) Patterns of association between genetic variability in apolipoprotein (apo) B, apo AI-CIII-AIV, and cholesterol ester transfer protein gene regions and quantitative variation in lipid and lipoprotein traits: influence of gender and exogenous hormones. Am J Hum Genet 50:92–106PubMedCentralPubMedGoogle Scholar
  23. 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 12:111–123PubMedCrossRefGoogle Scholar
  24. Knopman DS, Mosley TH, Catellier DJ, Coker LH, Atherosclerosis Risk in Communities Study Brain MRI Study (2009) Atherosclerosis Risk in Communities Study Brain MRI Study. Fourteen-year longitudinal study of vascular risk factors, APOE genotype, and cognition: the ARIC MRI Study. Alzheimers Dement 5(3):207–214PubMedCrossRefGoogle Scholar
  25. 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 Bio 17:560–568CrossRefGoogle Scholar
  26. Kulanuwat S, Phonrat B, Tungtrongchitr A, Limwongse C, Chongviriyaphan N, Tungtrongchitr R, Santiprabhob J (2014) Effects of PCSK1 genetic variants on obesity among Thai children and their family members: in relation to health risk, and biochemical and anthropometric parameters. Southeast Asian J Trop Med Public Health 45(1):214–225PubMedGoogle Scholar
  27. Lai CL, Liou LM, Liu CK, Yang YH, Lin RT (2014) Effects of metabolic syndrome, apolipoprotein E, and CYP46 on cognition among Taiwanese Chinese. Kaohsiung J Med Sci 30:343–349PubMedCrossRefGoogle Scholar
  28. Lee MJ, Chien KL, Chen MF, Stephenson DA, Su TC (2013) Overweight modulates APOE and APOA5 alleles on the risk of severe hypertriglyceridemia. Clin Chim Acta 416:31–35PubMedCrossRefGoogle Scholar
  29. Li TY, Zhang C, Asselbergs FW, Qi L, Rimm E, Hunter DJ, Hu FB (2007) Interaction between dietary fat intake and the cholesterol ester transfer protein TaqIB polymorphism in relation to HDL-cholesterol concentrations among US diabetic men. Am J Clin Nutr 86(5):1524–1529PubMedGoogle Scholar
  30. Liu S, Schmitz C, Stampfer MJ, Sacks F, Hennekens CH, Lindpaintner K, Ridker PM (2002) A prospective study of TaqIB polymorphism in the gene coding for cholesteryl ester transfer protein and risk of myocardial infarction in middle-aged men. Atherosclerosis 161(2):469–474PubMedCrossRefGoogle Scholar
  31. Lu Y, Tayebi N, Li H, Saha N, Yang H, Heng CK (2013) Association of CETP Taq1B and -629C > A polymorphisms with coronary artery disease and lipid levels in the multi-ethnic Singaporean population. Lipids Health Dis 12:85. doi: 10.1186/1476-511X-12-85 PubMedCentralPubMedCrossRefGoogle Scholar
  32. Luptakova L, Sivakova D, Cvicelova M, Wsólová L, Danková Z, Michnová A, Blažíček P (2013) Power of biomarkers and their relative contributions to metabolic syndrome in Slovak adult women. Ann Hum Biol 40:132–138PubMedCrossRefGoogle Scholar
  33. Mahley RW, Rall SC Jr (2000) Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet 1:507–537PubMedCrossRefGoogle Scholar
  34. Meena K, Misra A, Panday RM, Luthra K (2007) CETP TaqIB polymorphisms and CETP activity in normolipidemic healthy northern Indians. Diabetes Metab Syndr 1:239–244CrossRefGoogle Scholar
  35. Mitchell RJ, Earl L, Williams J, Bisucci T, Gasiamis H (1994) Polymorphisms of the gene coding for the cholesteryl ester transfer protein and plasma lipid levels in Italian and Greek migrants to Australia. Hum Biol 66:13–25PubMedGoogle Scholar
  36. Mohrschladt MF, van der Sman-de Beer F, Hofman MK, van der Krabben M, Westendorp RG, Smelt AH (2005) TaqIB polymorphism in CETP gene: the influence on incidence of cardiovascular disease in statin-treated patients with familial hypercholesterolemia. Eur J Hum Genet 13:877–882PubMedCrossRefGoogle Scholar
  37. Niu W, Zhang X, Qi Y (2012) Association of an apolipoprotein E polymorphism with circulating cholesterols and hypertension: a meta-based Mendelian randomization analysis. Hypertens Res 35:434–440PubMedCrossRefGoogle Scholar
  38. Novotny D, Vaverkova H, Karasek D, Malina P (2014) Genetic variants of apolipoprotein A5 T-1131C and apolipoprotein E common polymorphisms and their relationship to features of metabolic syndrome in adult dyslipidemic patients. Clin Biochem. doi: 10.1016/j.clinbiochem.2014.03.015 PubMedGoogle Scholar
  39. Olivieri O, Martinelli N, Bassi A, Trabetti E, Girelli D, Pizzolo F, Friso S, Pignatti PF, Corrocher R (2007) ApoE epsilon2/epsilon3/epsilon4 polymorphism, ApoC-III/ApoE ratio and metabolic syndrome. Clin Exp Med 7:164–172PubMedCrossRefGoogle Scholar
  40. Ordovas JM, Cupples LA, Corella D, Otvos JD, Osgood D, Martinez A, Lahoz C, Coltell O, Wilson PW, Schaefer EJ (2000) Association of cholesteryl ester transfer protein-TaqIB polymorphism with variations in lipoprotein subclasses and coronary heart disease risk: the Framingham study. Arterioscler Thromb Vasc Biol 20:1323–1329PubMedCrossRefGoogle Scholar
  41. Ozsait B, Kömürcü Bayrak E, Poda M, Can G, Hergenç G, Onat A, Humphries SE, Erginel Unaltuna N (2008) CETP TaqIB polymorphism in Turkish adults: association with dyslipidemia and metabolic syndrome. Anadolu Kardiyol Derg 8(5):324–330PubMedGoogle Scholar
  42. Ranjith N, Pegoraro RJ, Rom L (2009) Lipid profiles and associated gene polymorphisms in young Asian Indian patients with acute myocardial infarction and the metabolic syndrome. Metab Syndr Relat Disord 7:571–578PubMedCrossRefGoogle Scholar
  43. Ruan X, Ma L, Wang S, Lindpaintner K, Liu X, Wang B, Peng Z, Ma X, Cheng M, Zhang J, Liu L, Wang X (2009) Association of two CETP polymorphisms with HDL levels in the Chinese obese population. Obesity (Silver Spring) 17(12):2196–2201CrossRefGoogle Scholar
  44. 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):919–922CrossRefGoogle Scholar
  45. Sima A, Iordan A, Stancu C (2007) Apolipoprotein E polymorphism—a risk factor for metabolic syndrome. Clin Chem Lab Med 45:1149–1153PubMedCrossRefGoogle Scholar
  46. Suriyaprom K, Phonrat B, Namjuntra P, Harnroongroj T, Tungtrongchitr R (2010) The -11377C > G adiponectin gene polymorphism alters the adiponectin concentration and the susceptibility to type 2 diabetes in Thais. Int J Vitam Nutr Res 80(3):216–224PubMedCrossRefGoogle Scholar
  47. Suriyaprom K, Phonrat B, Tungtrongchitr R (2014a) Association of adiponectin gene -11377C > G polymorphism with adiponectin levels and the metabolic syndrome in Thais. Asia Pac J Clin Nutr 23(1):167–173PubMedGoogle Scholar
  48. Suriyaprom K, Tungtrongchitr R, Thawnasom K (2014b) Measurement of the levels of leptin, BDNF associated with polymorphisms LEP G2548A, LEPR Gln223Arg and BDNF Val66Met in Thai with metabolic syndrome. Diabetol Metab Syndr 6(1):6. doi: 10.1186/1758-5996-6-6 PubMedCentralPubMedCrossRefGoogle Scholar
  49. Tangjittipokin W, Chongjarean N, Plengvidhya N, Homsanit M, Yenchitsomanus PT (2012) Transcription factor 7-like 2 (TCF7L2) variations associated with earlier age-onset of type 2 diabetes in Thai patients. J Genet 91(2):251–255PubMedCrossRefGoogle Scholar
  50. Tanrikulu-Kucuk S, Ademoglu E, Gurdol F, Bilge AK, Mutlu-Turkoglu U, Nisanci Y (2010) Cholesteryl ester transfer protein Taq1B polymorphism in an angiographically assessed Turkish population: no effects on coronary artery disease risk. Genet Test Mol Biomarkers 14(5):637–642PubMedCrossRefGoogle Scholar
  51. Taylor JY, Kraja AT, de Las Fuentes L, Stanfill AG, Clark A, Cashion A (2013) An overview of the genomics of metabolic syndrome. J Nurs Scholarsh 45(1):52–59PubMedCentralPubMedCrossRefGoogle Scholar
  52. Tenkanen H, Koshinen P, Kontula K, Aalto-Setälä K, Mänttäri M, Manninen V, Runeberg SL, Taskinen MR, Ehnholm C (1991) Polymorphisms of the gene encoding cholesterol ester transfer protein and serum lipoprotein levels in subjects with and without coronary heart disease. Hum Genet 87:574–578PubMedCrossRefGoogle Scholar
  53. Vohl MC, Lamarche B, Pascot A, Leroux G, Prud’homme D, Bouchard C, Nadeau A, Després JP (1999) Contribution of the cholesteryl ester transfer protein gene TaqIB polymorphism to the reduced plasma HDL-cholesterol levels found in abdominal obese men with the features of the insulin resistance syndrome. Int J Obes Relat Metab Disord 23(9):918–925PubMedCrossRefGoogle Scholar
  54. Wilson PW, D’Agostino RB, Parise H, Sullivan L, Meigs JB (2005) Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation 112:3066–3072PubMedCrossRefGoogle Scholar
  55. Yijiang Z, Ruixing Y, Yiyang L, Yaju D, Shangling P, Weixiong L, Dezhai Y (2008) Association of TaqIB polymorphism in the cholesteryl ester transfer protein gene with serum lipid levels in the Guangxi Hei Yi Zhuang and Han populations. Investig Med 56(6):847–857Google Scholar
  56. Yilmaz H, Agachan B, Karaali ZE, Isbir T (2004) Taq1B polymorphism of CETP gene on lipid abnormalities in patients with type II diabetes mellitus. Int J Mol Med 13(6):889–893PubMedGoogle Scholar
  57. Zivelin A, Rosenberg N, Peretz H, Amit Y, Kornbrot N, Seligsohn U (1997) Improved Method for Genotyping Apolipoprotein E Polymorphisms by a PCR-Based Assay Simultaneously Utilizing Two Distinct Restriction Enzymes. Clin Chem 43:1657–1659PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Nutjaree Jeenduang
    • 1
    Email author
  • Sureerut Porntadavity
    • 2
  • Manit Nuinoon
    • 1
  • Dararat Horpet
    • 3
  • Nongyao Thepkwan
    • 4
  • Pattamawadee Thaworn
    • 4
  • Suporn Theanmontri
    • 5
  1. 1.School of Allied Health Sciences and Public HealthWalailak UniversityNakhon Si ThammaratThailand
  2. 2.Department of Clinical Chemistry, Faculty of Medical TechnologyMahidol UniversityBangkokThailand
  3. 3.Center for Scientific and Technological EquipmentsWalailak UniversityNakhon Si ThammaratThailand
  4. 4.Clinical Chemistry LaboratoryPhatthalung HospitalPhatthalungThailand
  5. 5.Occupational Medicine DepartmentPhatthalung HospitalPhatthalungThailand

Personalised recommendations