Polymorphisms of the gene encoding cholesterol ester transfer protein and serum lipoprotein levels in subjects with and without coronary heart disease

Tenkanen, H; Koskinen, Pekka; Kontula, Kimmo; Aalto‐Setälä, Katriina; Mänttäri, Matti; Manninen, Vesa; Runeberg, Sirkka-Liisa; Taskinen, Marja‐Riitta; Ehnholm, Christian

doi:10.1007/bf00209015

Cited by 60 publications

(45 citation statements)

References 29 publications

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“…Despite significant differences in mean HDL cholesterol levels between sexes (male subjects: 1.15 mmol/l; female subjects: 1.39 mmol/l; P Ͻ 0.0001, Mann-Whitney U test), there was no significant correlation between sex and the prevalence of macrovascular complications. In accordance with the present results, Tenkanen et al (18) mentioned that there was no difference even when the sexes were analyzed separately. In contrast, Kauma et al (19) showed that the association between the TaqIB polymorphism and HDL cholesterol was seen only in women, and Durlach et al (12) reported that the TaqIB polymorphism seems to exert a modulating role in men only.…”

supporting

confidence: 93%

Relationship Between TaqIB Cholesteryl Ester Transfer Protein Gene Polymorphism and Macrovascular Complications in Japanese Patients With Type 2 Diabetes

et al. 2002

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Cholesteryl ester transfer protein (CETP) is a key regulating factor of lipid metabolism, and the polymorphism of its gene may therefore be a candidate for modulating the lipid parameters, altering the susceptibility to atherosclerosis in type 2 diabetic subjects. In a group of 443 unrelated Japanese patients with type 2 diabetes, we studied the B1B2 polymorphism at the CETP locus, which is detectable with the restriction enzyme TaqI. Patients were separated into three groups according to genotype and compared based on their clinical characteristics, lipid parameters, and macrovascular complications. The B2 allele was associated in a dose-dependent fashion with higher HDL cholesterol and apolipoprotein AI levels, together with lower CETP concentrations. Furthermore, the prevalence of macrovascular complications, such as coronary heart disease, arteriosclerosis obliterans, and cerebral vascular disease, was significantly higher in subjects with the B1B1 genotype. Multiple logistic regression analysis also showed that the B1 allele of CETP genotype was associated with the incidence of these three complications independently of other risk factors. Thus, in type 2 diabetic patients, the B1B2 polymorphism of CETP gene is likely to be a strong genetic predictor of macrovascular complications. Diabetes 51:871-874, 2002 T ype 2 diabetic patients are at high risk of atherosclerotic diseases, such as coronary heart disease (CHD), cerebral vascular disease (CVD), or arteriosclerosis obliterans (ASO) (1). This increased risk can be partly accounted for by the lipoprotein disorders linked to insulin resistance: elevated VLDL, triglycerides, and cholesterol, together with low HDL cholesterol (2). The inverse relationship between the level of HDL cholesterol and the risk of cardiovascular disease is commonly explained by the crucial role of HDL in reverse cholesterol transport (3-5). By this process, cholesterol from peripheral cells is taken up by HDL and transported to the liver, where it is metabolized and excreted in the bile. Cholesteryl ester transfer protein (CETP) has a central role in the metabolism of HDL lipoprotein and may therefore alter the susceptibility to atherosclerotic vascular disease (3). In a normolipidemic population, the plasma CETP concentration varies mostly over a threefold range and is influenced by environmental factors (6). Plasma CETP has been shown to be elevated in smokers and to be decreased by heavy alcohol drinking and physical training (7-9).Recently, the B1B2 polymorphism of intron 1 of the CETP gene (presence or absence of a TaqIB restriction site) was shown to be a determinant of HDL cholesterol (10). It has been reported that both healthy and type 2 diabetic subjects with the B2B2 genotype of TaqIB polymorphism have significantly higher HDL cholesterol levels than those with the B1B1 or B1B2 genotype (11,12). Furthermore, in subjects with the B2B2 genotype, the progression of coronary atherosclerosis is more greatly suppressed by pravastatin than in those with the B1B1 or B1B2 genotype,...

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confidence: 93%

Relationship Between TaqIB Cholesteryl Ester Transfer Protein Gene Polymorphism and Macrovascular Complications in Japanese Patients With Type 2 Diabetes

et al. 2002

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“…These results are in agreement with previously reported effects of the TaqIB polymorphism in different populations. 5 ± 11 However, studies in Finland 46 and Sri Lanka 47 found weak or no association between the CETP-TaqIB polymorphism and plasma HDLchol concentrations. In the present study, thè expected raising effect' of the B2 allele was abolished when indices of obesity and of AT distribution were taken into account.…”

Section: Discussionmentioning

confidence: 99%

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

Vohl¹,

Lamarche²,

Pascot³

et al. 1999

Int J Obes

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OBJECTIVE: The aim of this study was to examine the relation between the CETP-TaqIB polymorphism and reduced plasma HDL-cholesterol levels commonly observed among men characterized by abdominal obesity and features of the insulin resistance syndrome. SUBJECTS: A total of 187 sedentary men, non-smokers and free from metabolic disorders were classi®ed on the basis of their CETP-TaqIB genotype. RESULTS: Plasma HDL and HDL 3 -cholesterol concentrations as well as the CETP activity were signi®cantly different between the three genotypes, B1B1 men having signi®cantly lower HDL and HDL 3 -cholesterol levels and higher CETP activity than B2B2 homozygotes. A 2Â3 ANOVA was used to determine the source of variation of plasma HDL and HDL 2 -cholesterol levels among the three genotypic groups of men divided on the basis of either a high ( ! 27 kgam 2 ) or a low (`27 kgam 2 ) BMI, a high ( ! 130 cm 2 ) or a low (`130 cm 2 ) accumulation of visceral adipose tissue assessed by computed tomography, or a low versus a high fasting plasma insulin concentration (using the median value as a cutoff point). The effect of the CETP genotype observed on plasma HDL-cholesterol concentrations was attenuated among men with features of the insulin resistance syndrome. It seems that the expected raising effect of the B2 allele on plasma HDL-cholesterol concentrations was blunted in the presence of a BMI ! 27 kgam 2 , a high accumulation of visceral adipose tissue or hyperinsulinaemia. CONCLUSION: Our data indicate that the CETP gene TaqIB polymorphism in¯uences plasma CETP activity on one hand and plasma HDL-cholesterol concentrations on the other hand among men. The association between the TaqIB polymorphism and plasma HDL-cholesterol concentrations is altered by the presence of abdominal obesity and some features of the insulin resistance syndrome.

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“…The less-common allele of this SNP has been shown to be associated with lower CETP and higher HDL levels across numerous studies and populations with highly significant P values (45,49,53,60,. Only in studies with small test populations has neither CETP nor HDL been affected in a statistically significant manner (43,(93)(94)(95)(96)(97)(98)(99)(100)(101)(102)(103)(104)(105)(106)(107). Since it is not immediately apparent how this SNP could modulate CETP expression, it has long been suspected that this SNP is linked with another change that more directly affects expression.…”

Section: Wild-type Proteinmentioning

confidence: 99%

“…As with I405V, the Taq1B studies were subjected to a formal meta-analysis as described above. Data were excluded if they reported data on subjects specifically selected by abnormal lipid criteria (68,69,77,83,88,107), on alcoholics (75), on related individuals (91), and specifically on patients with non-CAD related disease (76,78). Duplicate publications and publications with patient overlap were excluded.…”

Section: Wild-type Proteinmentioning

confidence: 99%

Natural genetic variation as a tool in understanding the role of CETP in lipid levels and disease

Boekholdt

Thompson

2003

Journal of Lipid Research

153

117

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Since the identification of cholesteryl ester transfer protein (CETP), its role in the modulation of HDL levels and cardiovascular disease has been debated. With the early detection of genetic variants followed by the finding of families deficient in CETP, genetic studies have played a large role in the attempts to understand the association of CETP with lipids and disease; however, results of these studies have often led to disparate conclusions. With the availability of a greater variety of genetic polymorphisms and larger studies in which disease has been examined, it is now possible to compare the breadth of CETP genetic studies and draw better conclusions. The most broadly studied polymorphism is TaqIB for which over 10,000 individuals have been genotyped and had HDL levels determined. When these studies are subjected to a meta-analysis, the B2B2 homozygotes are found to have higher HDL levels than B1B1 homozygotes (0.12 mmol/l, 95% CI ‫؍‬ 0.11-0.13, P Ͻ 0.0001). A similar analysis of the I405V polymorphism yields 0.05 mmol/l higher HDL levels in 405VV homozygotes than in 405II homozygotes (95% CI ‫؍‬ 0.03-0.07, P Ͻ 0.0001). The implications of these studies for cardiovascular disease will be addressed. -Boekholdt, S. M., and J. F. Thompson. Natural genetic variation as a tool in understanding the role of CETP in lipid levels and disease. J. Lipid Res. 2003. 44: 1080-1093.

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Polymorphisms of the gene encoding cholesterol ester transfer protein and serum lipoprotein levels in subjects with and without coronary heart disease

Cited by 60 publications

References 29 publications

Relationship Between TaqIB Cholesteryl Ester Transfer Protein Gene Polymorphism and Macrovascular Complications in Japanese Patients With Type 2 Diabetes

Relationship Between TaqIB Cholesteryl Ester Transfer Protein Gene Polymorphism and Macrovascular Complications in Japanese Patients With Type 2 Diabetes

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

Natural genetic variation as a tool in understanding the role of CETP in lipid levels and disease

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