DNA Polymorphisms of the Cholesteryl Ester Transfer Protein (CETP) Gene in Italian and Greek Migrants to Australia

Mitchell, Robert J.; Earl, Lucy; Bisucci, Teresa; Gasiamis, H; Williams, John

doi:10.1159/000154195

Cited by 22 publications

(34 citation statements)

References 8 publications

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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%

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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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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“…It has been suggested that these associations may be population related (Tenkanen et al, 1991;Mitchell et al, 1994) and highly influenced by environmental factors, such as tobacco smoking (Kauma et al, 1996). Also, Kuivenhoven et al (1998) showed interactions between the TaqI genotype and the progression of coronary heart disease (CHD) after therapy.…”

Section: Introductionmentioning

confidence: 99%

TaqI B1/B2 and -629A/C cholesteryl ester transfer protein (CETP) gene polymorphisms and their association with CETP activity and high-density lipoprotein cholesterol levels in a Tehranian population. Part of the Tehran Lipid and Glucose Study (TLGS)

Daneshpour

Hedayati

2007

Genet. Mol. Biol.

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We examined the cholesteryl ester transfer protein (CETP) gene TaqI intron 1 B1/B2 polymorphism and the -629A/C CETP promoter polymorphism in respect to high-density lipoprotein cholesterol (HDL-C) in a healthy Iranian population taken from the Tehran Lipid and Glucose Study (TLGS). The relationship between CETP activity and HDL-C level was also determined along with body mass index, blood pressure and tobacco smoking status. PCR-RFLP used to amplify a segment of the CETP intron 1 TaqI (B2/B1) polymorphism from 1021 individuals and we selected 345 individuals from the lowest, middle and highest HDL-C deciles and investigated the -629A/C polymorphism. We also evaluated the CETP activity of 103 of these individuals, each with at least one homozygous allele. The presence of the TaqI B2 and -629A/C A alleles were significantly associated with increased HDL-C levels (B2B2 = 1.19 ± 0.31 mmolL -1 vs. B1B1 = 1.01 ± 0.2 mmol L -1 for p < 0.001; AA = 1.15 ± 0.41 mmol L -1 vs. CC = 0.95 ± 0.28 mmol L -1 for p < 0.001) and decreased the CETP activity (B1B1 = 67.8 ± 8.9 pmol L -1 vs. B2B2 = 62.6 ± 9.6 pmol L -1 for p < 0.01; CC = 68.6 ± 8.4 pmol L -1 vs. AA = 62.7 ± 9.7 pmol L -1 for p < 0.002). The frequencies were 0.382 for the TaqI B2 allele and 0.462 for the -629A/C A allele, with linkage disequilibrium analysis giving D = 0.0965 and D' = 0.4695. We demonstrated that the TaqI B1 and B2 alleles and the -629A/C A and C alleles were in linkage disequilibrium in our population and that there was a significant association between the B2 and A alleles and high HDL-C levels and low CETP activity. Linkage disequilibrium between the TaqI A and B2 alleles also detected.

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confidence: 99%

“…10 The B2 allele (absence of the TaqI restriction site) at this polymorphic site has been associated in normolipemic subjects with increased HDL cholesterol (HDL-C) levels and decreased CETP activity and levels, [13][14][15][16] thus resembling a mild form of CETP deficiency. It has been suggested that this association may be population specific 17,18 and highly influenced by environmen-tal factors, such as alcohol consumption and tobacco smoking. 15,19,20 Moreover, Kuivenhoven et al 21 have shown an interaction between the TaqIB genotype and the progression of coronary heart disease (CHD) after therapy.…”

mentioning

confidence: 99%

Association of Cholesteryl Ester Transfer Protein– Taq IB Polymorphism With Variations in Lipoprotein Subclasses and Coronary Heart Disease Risk

Ordovás

Cupples

Corella

et al. 2000

ATVB

365

250

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Abstract-Cholesteryl ester transfer protein (CETP) facilitates the exchange of triglycerides and cholesteryl esters between lipoprotein particles, a key step in reverse cholesterol transport in humans. Variations at the CETP locus have been shown to be determinants of the levels and activity of CETP and high density lipoprotein (HDL) plasma concentration. The associations of the common CETP polymorphism, TaqIB in intron 1, with lipoprotein levels and particle size distribution, CETP activity, and coronary heart disease (CHD) risk were examined in a population-based sample of 1411 men and 1505 women from the Framingham Offspring Study. The B2 allele frequency was 0.444 in men and 0.433 in women, and its presence was significantly (PϽ0.05) associated with decreased CETP activity. B1B1 men had lower HDL cholesterol (HDL-C) levels (1.07 mmol/L) compared with B1B2 (1.14 mmol/L) and B2B2 (1.18 mmol/L) men (PϽ0.001). Likewise, B1B1 women had lower HDL-C levels (1.40 mmol/L) compared with B1B2 (1.46 mmol/L) and B2B2 (1.53 mmol/L) women (PϽ0.001). In men, the B2 allele was associated with increased particle size for HDL and low density lipoprotein. In women, a similar effect was demonstrated only for HDL particle size. The odds ratio for prevalent CHD associated with the B2 allele was 0.696 (Pϭ0.035) in men. After adjusting for age, body mass index, systolic blood pressure, diabetes, smoking, alcohol consumption, ␤-blocker use, total cholesterol, and HDL-C, this odds ratio was 0.735 (Pϭ0.187), suggesting that the protective effect of the B2 allele was due in part to its association with HDL-C levels. No significant protective effects were observed in women. These data demonstrate that variation at the CETP gene locus is a significant determinant of HDL-C levels, CETP activity, and lipoprotein size in this population. Moreover, these effects appear to translate into a lower CHD risk among those men with the B2 allele. Key Words: cholesteryl ester transfer protein Ⅲ coronary heart disease Ⅲ lipoproteins Ⅲ gene polymorphisms C holesteryl ester transfer protein (CETP) facilitates the exchange of triglycerides and cholesteryl esters between lipoprotein particles. In humans, CETP mRNA encodes a polypeptide of M r 53 000, which is n-glycosylated at 4 sites, giving rise to the mature form of CETP of M r 74 000. 1 CETP is expressed primarily in liver, spleen, and adipose tissue, and lower levels have been detected in the small intestine, adrenal gland, heart, kidney, and skeletal muscle. 1,2 The CETP gene encompasses 16 exons, and it has been localized on chromosome 16q21 adjacent to the lecithin-cholesterol acyltransferase gene. Several mutations at the CETP locus have been identified, resulting in the absence of detectable CETP mass and/or activity. 3 These mutations are common in Japanese populations, 4 -7 although some have been recently reported in white subjects. 8,9 CETP deficiency is associated with hyperalphalipoproteinemia, which is primarily due to an increase of cholesteryl ester-enriched large-sized HDL. Conversely, ...

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DNA Polymorphisms of the Cholesteryl Ester Transfer Protein (CETP) Gene in Italian and Greek Migrants to Australia

Cited by 22 publications

References 8 publications

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

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

TaqI B1/B2 and -629A/C cholesteryl ester transfer protein (CETP) gene polymorphisms and their association with CETP activity and high-density lipoprotein cholesterol levels in a Tehranian population. Part of the Tehran Lipid and Glucose Study (TLGS)

Association of Cholesteryl Ester Transfer Protein– Taq IB Polymorphism With Variations in Lipoprotein Subclasses and Coronary Heart Disease Risk

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