Abstract
Associations between the TAQIB and I405V polymorphisms and obesity risk were studied for a single locus as well as in combination. A total of 934 obese subjects and 924 normal controls were included in the study. TAQIB was associated with high-density lipoprotein (HDL) levels (P < 0.001), while I405V was associated with levels of low-density lipoprotein (P = 0.03) and total cholesterol (P = 0.007). Less common alleles of TAQIB and I405V were associated with decreased obesity risk and further drops in odds ratio (OR) were observed in carriers with rare homozygous alleles on both loci (OR = 0.659, P = 0.02). The TAQIB B2 allele was associated with reductions in both hip circumference (P = 0.034) and triceps skinfold thickness (TST) (P = 0.045), although this effect was completely abolished after controlling for HDL levels. The 405V variant was associated with reductions in hip circumference (P = 0.031), body fat composition (P = 0.039) and TST (P = 0.036); these effects were weakened (P < 0.1) after controlling for HDL levels. In conclusion, less common alleles of TAQIB and I405V appear to be modestly associated with obesity risk in an adult Chinese population. Adjustments for HDL levels completely (TAQIB) or partially (I405V) abolished the observed association.
Similar content being viewed by others
References
Drayna D, Jarnagin AS, McLean J et al (1987) Cloning and sequencing of human cholesteryl ester transfer protein cDNA. Nature 327:632–634
Barter PJ (2002) Hugh Sinclair lecture: the regulation and remodelling of HDL by plasma factors. Atheroscler Suppl 3:39–47
Lamarche B, Uffelman KD, Carpentier A et al (1999) Triglyceride enrichment of HDL enhances in vivo metabolic clearance of HDL apo A-I in healthy men. J Clin Invest 103:1191–1199
Van der Steeg WA, Kuivenhoven JA, Klerkx AH, Boekholdt SM, Hovingh GK, Kastelein JJ (2004) Role of CETP inhibitors in the treatment of dyslipidemia. Curr Opin Lipidol 15:631–636
Whitlock ME, Swenson TL, Ramakrishnan R et al (1989) Monoclonal antibody inhibition of cholesteryl ester transfer protein activity in the rabbit. Effects on lipoprotein composition and high density lipoprotein cholesteryl ester metabolism. J Clin Invest 84:129–137
Abbey M, Calvert GD (1989) Effects of blocking plasma lipid transfer protein activity in the rabbit. Biochim Biophys Acta 1003:20–29
Benoist F, Lau P, McDonnell M, Doelle H, Milne R, McPherson R (1997) Cholesteryl ester transfer protein mediates selective uptake of high density lipoprotein cholesteryl esters by human adipose tissue. J Biol Chem 272:23572–23577
Jiang XC, Moulin P, Quinet E et al (1991) Mammalian adipose tissue and muscle are major sources of lipid transfer protein mRNA. J Biol Chem 266:4631–4639
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 24:188–194
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 14:1129–1136
Hayashibe H, Asayama K, Nakane T, Uchida N, Kawada Y, Nakazawa S (1997) Increased plasma cholesteryl ester transfer activity in obese children. Atherosclerosis 129:53–58
Vassiliou G, McPherson R (2004) Role of cholesteryl ester transfer protein in selective uptake of high density lipoprotein cholesteryl esters by adipocytes. J Lipid Res 45:1683–1693
Kondo I, Berg K, Drayna D, Lawn R (1989) DNA polymorphism at the locus for human cholesteryl ester transfer protein (CETP) is associated with high density lipoprotein cholesterol and apolipoprotein levels. Clin Genet 35:49–56
Gudnason V, Kakko S, Nicaud V et al (1999) Cholesteryl ester transfer protein gene effect on CETP activity and plasma high-density lipoprotein in European populations. The EARS Group. Eur J Clin Invest 29:116–128
Ikewaki K, Mabuchi H, Teramoto T et al (2003) Association of cholesteryl ester transfer protein activity and TaqIB polymorphism with lipoprotein variations in Japanese subjects. Metabolism 52:1564–1570
Brousseau ME, O’Connor JJ Jr, Ordovas JM et al (2002) Cholesteryl ester transfer protein TaqI B2B2 genotype is associated with higher HDL cholesterol levels and lower risk of coronary heart disease end points in men with HDL deficiency: Veterans Affairs HDL Cholesterol Intervention Trial. Arterioscler Thromb Vasc Biol 22:1148–1154
Barzilai N, Atzmon G, Schechter C et al (2003) Unique lipoprotein phenotype and genotype associated with exceptional longevity. JAMA 290:2030–2040
Rose GA, Blackburn H, Gillum RF, Prineas RJ (1982) Cardiovascular survey methods. WHO Monogr Ser 56:162–165
Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502
Helms C (1990) Method: manual isolation of human DNA from lymphoblasts or whole blood. CRI laboratory manual: RFLPs project
Fumeron F, Betoulle D, Luc G et al (1995) Alcohol intake modulates the effect of a polymorphism of the cholesteryl ester transfer protein gene on plasma high density lipoprotein and the risk of myocardial infarction. J Clin Invest 96:1664–1671
Gerholm-Larsen B, Nordestgaard BG, Steffensen R, Jensen G, Tybjaerg-Hansen A (2000) Elevated HDL cholesterol is a risk factor for ischemic heart disease in white women when caused by a common mutation in the cholesteryl ester transfer protein gene. Circulation 101:1907–1912
Takahashi K, Jiang XC, Sakai N et al (1993) A missense mutation in the cholesteryl ester transfer protein gene with possible dominant effects on plasma high density lipoproteins. J Clin Invest 92:2060–2064
Sandhofer A, Tatarczyk T, Laimer M et al (2008) The Taq1B-variant in the cholesteryl ester-transfer protein gene and the risk of metabolic syndrome. Obesity (Silver Spring) 16:919–922
Huang ZY, Guo HW, Xu ZH, Xue K (2006) Association of gene polymorphism at cholesterol ester transfer protein locus with obesity and response to dietary intervention in obesity. Wei Sheng Yan Jiu 35:447–449
Srivastava N, Achyut BR, Prakash J, Agarwal CG, Pant DC, Mittal B (2008) Association of cholesteryl ester transfer protein (TaqIB) and apolipoprotein E (HhaI) gene variants with obesity. Mol Cell Biochem 314:171–177
Lu H, Inazu A, Moriyama Y et al (2003) Haplotype analyses of cholesteryl ester transfer protein gene promoter: a clue to an unsolved mystery of TaqIB polymorphism. J Mol Med 81:246–255
Frisdal E, Klerkx AH, Le GW et al (2005) Functional interaction between −629C/A, −971G/A and −1337C/T polymorphisms in the CETP gene is a major determinant of promoter activity and plasma CETP concentration in the REGRESS Study. Hum Mol Genet 14:2607–2618
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 20:507–515
Teran-Garcia M, Despres JP, Tremblay A, Bouchard C (2008) Effects of cholesterol ester transfer protein (CETP) gene on adiposity in response to long-term overfeeding. Atherosclerosis 196:455–460
Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH (2006) Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med 354:1264–1272
Green C, Oncley JL, Karnovsky ML (1960) Lipid composition of lipoproteins of normal human plasma. J Biol Chem 235:2884–2888
Festa A, D’Agostino R Jr, Mykkanen L et al (1999) LDL particle size in relation to insulin, proinsulin, and insulin sensitivity. The Insulin Resistance Atherosclerosis Study. Diabetes Care 22:1688–1693
Hulthe J, Bokemark L, Wikstrand J, Fagerberg B (2000) The metabolic syndrome, LDL particle size, and atherosclerosis: the Atherosclerosis and Insulin Resistance (AIR) study. Arterioscler Thromb Vasc Biol 20:2140–2147
Tall AR (1990) Plasma high density lipoproteins. Metabolism and relationship to atherogenesis. J Clin Invest 86:379–384
Acknowledgments
We would like to thank the community, particularly the participants, for taking part in this study. We appreciate the invaluable help of associates in collecting of blood samples and biochemical analyses. This study was supported by the Beijing Hypertension League Institute, in part through an unrestricted educational grant from F. Hoffmann-La Roche, the National Infrastructure Program of Chinese Genetic Resources (2005DKA21300), and the Tsinghua-Yuyuan Medical Science Research Foundation.
Conflict of interest statement
The authors declare no conflicts of interest associated with this manuscript.
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Ruan, X., Ma, L., Wang, S. et al. TAQIB and I405V polymorphisms of CETP are moderately associated with obesity risk in the Chinese adult population. Acta Diabetol 47, 217–224 (2010). https://doi.org/10.1007/s00592-009-0117-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00592-009-0117-4