Lack of Association Between the Cholesteryl Ester Transfer Protein Gene—TaqIB Polymorphism and Coronary Restenosis Following Percutaneous Transluminal Coronary Angioplasty and Stenting: A Pilot Study

Abstract

Background: The most widely studied variation at the cholesteryl ester transfer protein (CETP) gene locus is a silent base change called the Thermobius aquaticus IB (TaqIB) polymorphism. TaqIB has been shown to affect levels/activity of CETP, plasma levels of high-density lipoprotein cholesterol (HDL-C), and to contribute to the risk of developing atherosclerosis and coronary heart disease (CHD). Ongoing studies are investigating possible associations between CETP gene polymorphisms and the development of coronary restenosis following percutaneous transluminal coronary angioplasty (PTCA) and stenting.

Methods and Results: The primary objective of the present study was to investigate the frequency of TaqIB-polymorphism, and a possible association with post-PTCA coronary restenosis, in 204 Greek patients who had undergone PTCA and stenting. As a secondary objective, the analysis was extended to explore possible interacting or additive effects by various CHD risk factors, and a deletion in the α_2B-adrenergic receptor gene. The frequency of TaqIB was 54%, similar to the frequency of the polymorphism in a group of 35 healthy controls.

Conclusions: The results from this study do not indicate that the TaqIB variation at the CETP gene locus is a significant predictor for assessing the risk of developing coronary restenosis following PTCA and stenting. This result was not affected when considering any one of the additionally studied factors.

Keywords

CETP coronary angioplasty coronary stents restenosis gene polymorphism

Get full access to this article

View all access options for this article.

References

White DA , Baxter M. Hormones and Metabolic Control. 2nd ed. London: Arnold; 1994.

Kuivenhoven JA , de Knijff P. , Boer JMA , et al. Heterogeneity at the CETP gene locus-Influence on plasma CETP concentrations and HDL cholesterol levels. Arterioscler Thromb Vasc Biol. 1997 ;17(3):560-568.

Ordovas JM , Cupples A. , Corella D. , et al. Association of cholesteryl ester transfer protein-TaqIB polymorphism with variations in lipoprotein subclasses and coronary heart disease risk . The Framingham Study. Thromb Vasc Biol. 2000;20(5):1323-1329.

Al-Daghri NM , Al- Attas O. , Patel A. , et al. Association between the cholesteryl ester transfer protein TaqI-detectable B polymorphism and low high-density lipoprotein cholesterol concentration in Saudis. Clin Sci . 2003;105(4):467-472.

Kuivenhoven JA , Jukema W. , Zwinderman AH , et al. The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis . N Engl J Med. 1998;338(2):86-93.

Boer JMA , Feskens EJM , Kuivenhoven JA , et al. Parental history of myocardial infarction: lipid traits, gene polymorphisms and life-style. Atherosclerosis . 2001;155(1):149-156.

Gudnason V. , Kakko S. , Nicaud V. , et al. Cholesteryl ester transfer protein gene effect on CETP activity and plasma high-density lipoprotein in European populations. Eur J Clin Invest. 1999;29(2):116-128.

Hannuksela ML , Liinamaa JM , Kesäniemi YA , Savolainen MJ Relation of polymorphisms in the cholesteryl ester transfer protein gene to transfer protein activity and plasma lipoprotein levels in alcohol drinkers. Atherosclerosis. 1994;110(1):35-44.

Kolovou GD , Anagnostopoulou KK , Mikhailidis DP The link between human and transgenic animal studies involving postprandial hypertriglyceridemia and CETP gene polymorphisms. Open Cardiovasc Med J. 2009 Jun 11;3:48-50.

10.

Anagnostopoulou KK , Kolovou GD , Kostakou PM , et al. Sex-associated effect of CETP and LPL polymorphisms on postprandial lipids in familial hypercholesterolaemia . Lipids Health Dis. 2009 Jun 26;8:24.

11.

Kolovou GD , Anagnostopoulou KK , Karyofillis P. , et al. Cholesteryl ester transfer protein gene polymorphisms and severity of coronary stenosis. Clin Invest Med. 2006 ;29(1):14-19.

12.

Anagnostopoulou K. , Kolovou G. , Kostakou P. , Mihas C. , Mikhailidis D. , Cokkinos DV Pharmacogenetic study of cholesteryl ester transfer protein gene and simvastatin treatment in hypercholesterolaemic subjects . Expert Opin Pharmacother . 2007;8(15):2459-2463.

13.

Cohen JC , Wang Z. , Grundy SM , Stoesz MR , Guerra R. Variation at the hepatic lipase and apolipoprotein AI/CIII/AIV loci is a major cause of genetically determined variation in plasma HDL cholesterol levels . J Clin Invest. 1994;94(6):2377-2384.

14.

Corbex M. , Poirier O. , Fumeron F. , et al. Extensive association analysis between the CETP gene and coronary heart disease phenotypes reveals several putative functional polymorphisms and gene-environment interaction. Genet Epidemiol. 2000;19(1):64-80.

15.

Radeau T. , Vohl MC , Houde I. , et al. HDL cholesterol and TaqIB cholesteryl ester transfer protein gene polymorphism in renal transplant recipients. Nephron . 2000;84(4):333-341.

16.

Vohl MC , Lamarche B. , Pascot A. , et al. 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. 1999;23(9):918-925.

17.

Kastrati A. , Dirschinger J. , Schomig A. Genetic risk factors and restenosis after percutaneous coronary interventions. Herz. 2000;25(1):34-46.

18.

Zee RY , Hoh J. , Cheng S. , et al. Multi-locus interactions predict risk for post-PTCA restenosis: an approach to the genetic analysis of common complex disease. Pharmacogenomics J. 2002;2(3):197-201.

19.

Zee RYL , Fernandez-Otiz A. , Macaya C. , Pintor E. , Lindpaintner K. , Fernandez-Cruz A. Lipid metabolism and occurrence of post-percutaneous transluminal coronary angioplasty restenosis: role of cholesteryl ester transfer protein and paraoxonase/arylesterase . J Thromb Haemost. 2003;1(6):1202-1207.

20.

Dangas G. , Kuepper F. Restenosis: repeat narrowing of a coronary artery. Circulation . 2002;105(22):2586-2591.

21.

Hamon M. , Amant C. , Bauters C. , et al. Dual determination of angiotensin converting enzyme and angiotensin-II type I receptor genotypes as predictors of restenosis after coronary angioplasty . Am J Cardiol. 1998;81(1):79-81.

22.

Heinonen P. , Jartti L. , Jarvisalo MJ , et al. Deletion polymorphism in the alpha2B-adrenergic receptor gene is associated with flow-mediated dilatation of the brachial artery. Clin Sci. 2002;103(5):517-524.

23.

Manolis AS , Patsouras N. , Ilias I. , et al. Lack of association between α2B-adrenergic receptor polymorphism and risk of restenosis following coronary angioplasty and stent implantation-preliminary report. Clin Chem Lab Med. 2006;44(7):807-812.

24.

Freeman DJ , Samanib NJ , Wilsona V. , et al. A polymorphism of the cholesteryl ester transfer protein gene predicts cardiovascular events in non-smokers in the West of Scotland Coronary Prevention Study. Eur Heart J. 2003;24(20):1833-1842.

25.

Tai E. , Ordovas J. , Corella D. , et al. 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. 2003;63(1): 19-30.

26.

Dullaart RP , Beusekamp BJ , Riemens SC , et al. High-density lipoprotein cholesterol is related to the TaqIB cholesteryl ester transfer protein gene polymorphism and smoking, but not to moderate alcohol consumption in insulin-dependent diabetic men. Scand J Clin Lab Invest . 1998 ;58(3):251-258.

27.

Richman JG , Regan JW 2-Adrenergic receptors increase cell migration and decrease F-actin labeling in rat aortic smooth muscle cells. Am J Physiol Cell Physiol . 1998;274(3 pt 1):C654-C662.

28.

Bauters C. , Hamon M. , van Belle E. , Dupuis B. , Lablanche JM , Bertrand ME Restenosis after angioplasty. Contribution of experimental models . Arch Mal Coeur Vaiss. 1993;86(spec no 1):47-56.

29.

Hannuksela ML , Marcel YL , Kesäniemi YA , Savolainen MJ Reduction in the concentration and activity of plasma cholesteryl ester transfer protein by alcohol. J Lipid Res. 1992;33(5):737-744.

30.

Freeman DJ , Griffin BA , Holmes AP , et al. Regulation of plasma HDL cholesterol & subfraction distribution by genetic & environmental factors. Associations between the TaqIB RFLP in the CETP gene and smoking and obesity. Arterioscler Thromb . 1994;14(3):336-344.

31.

Inazu A. , Koizumi J. , Kajinami K. , Kiyohar T. , Chichibu K. , Mabuchi H. Opposite effects on serum cholesteryl ester transfer protein levels between long-term treatments with pravastatin and probucol in patients with primary hypercholesterolemia and xanthoma. Atherosclerosis . 1999;145(2):405-413.

32.

Guérin M. , Dolphin PJ , Talussot C. , Gardette J. , Berthézéne F. , Chapman MJ Pravastatin modulates cholesteryl ester transfer from HDL to ApoB-containing lipoproteins and lipoprotein subspecies profile in familial hypercholesterolemia . Arterioscler Thromb Vasc Biol. 1995;15(9):1359-1368.

33.

Arai T. , Yamashita S. , Hirano K. , et al. Increased plasma cholesteryl ester transfer protein in obese subjects. A possible mechanism for the reduction of serum HDL cholesterol levels in obesity. Arterioscler Thromb Vasc Biol. 1994;14(7):1129-1136.

34.

Asayama K. , Hayashibe H. , Dobashi K. , et al. Increased serum cholesteryl ester transfer protein in obese children. Obes Res. 2002;10(6):439-446.

35.

Angerio AD , Fink DA New strategies in the prevention of restenosis. Crit Care Nurs Q. 2001;24(1):62-68.

36.

Ribichini F. , Ferrero V. , Matullo G. , et al. Association study of the I/D polymorphism and plasma ACE as risk factors for stent restenosis . Clin Sci. 2004;107(4):381-389.

37.

Splawski I. , Timothy KW , Tateyama M. , et al. Variant of SCN5A sodium channel implicated in risk of cardiac arrhythmia. Science. 2002 ;297(5585):1333-1336.

38.

Manolis AS , Chiladakis J. , Hahalis G. , Agelopoulos G. Initial experience with a newer generation coronary stent. J Invasive Cardiol. 2001;13(3):217-222.

39.

Manolis AS Reduced incidence of clinical restenosis with newer generation stents, stent oversizing and higher-pressure deployment: single-operator experience . Clin Cardiol. 2001; 24(2):119-126.