Sex difference in the regulation of plasma high density lipoprotein cholesterol by genetic and environmental factors

Kauma, Heikki; Mj, Savolainen; Heikkilä, Reino; Ao, Rantala; Lilja, M; Reunanen, Antti; Ya, Kesäniemi

doi:10.1007/bf02265258

Cited by 85 publications

(73 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[3][4][5]8,[35][36][37] In some reports, the association was seen only in subgroups, such as ex-and nonsmokers, 38 or in women, but not in men. 39 Alhough we could not replicate the association of an increased baseline HDL-C in the presence of the mutant B2 allele of SNP4, the strong stepwise decrease in CETP mass and activity associated with the number of B2 alleles of SNP4 clearly underlines such an expected effect on HDL-C. With respect to SNP 7 (A373P) and SNP8 (R451Q), the Copenhagen City Heart Study found a decrease in HDL-C and ApoA1 in carriers of the mutant allele, both in men and women. 11 Despite the low frequency of these mutant alleles, we also observed a significant decrease in HDL-C associated with the SNP7 (A373P) CETP polymorphism.…”

Section: Discussionmentioning

confidence: 99%

Haplotypes of the cholesteryl ester transfer protein gene predict lipid-modifying response to statin therapy

Winkelmann¹,

Hoffmann

Nauck

et al. 2003

Pharmacogenomics J

View full text Add to dashboard Cite

Cholesteryl ester transfer protein (CETP) plays a central role in high-density lipoprotein (HDL) metabolism. Single nucleotide polymorphisms (SNPs) and haplotypes in the CETP gene were determined in 98 patients with untreated dyslipidemias and analyzed for associations with plasma CETP and plasma lipids before and during statin treatment. Individual CETP SNPs and haplotypes were both significantly associated with CETP enzyme mass and activity. However, only certain CETP haplotypes, but not individual SNPs, significantly predicted the magnitude of change in HDL cholesterol (HDL-C) and triglycerides. After adjusting for covariates and multiple testing, the TTCAAA haplotype showed a gene-dose effect in predicting the HDL-C increase (P¼0.03), while the TTCAAAGGG and AAAGGG haplotypes predicted a decrease in triglycerides (P¼0.04 both). This is the first study to demonstrate that SNP haplotypes derived from allelic SNP combinations in the CETP gene were more informative than single SNPs in predicting the response to lipid-modifying therapy with statins. The Pharmacogenomics Journal (2003) 3, 284-296, doi:10.1038/sj.tpj.6500195Keywords: cholesteryl ester transfer protein; HDL-cholesterol; triglycerides; haplotype; single nucleotide polymorphism; statin INTRODUCTION Cholesteryl ester transfer protein (CETP) mediates the transfer of neutral lipids between lipoproteins and plays a central role in high-density lipoprotein (HDL) metabolism. CETP transfers cholesteryl esters associated with HDL to triglyceride-rich lipoproteins, facilitating the clearance of cholesteryl esters from plasma. 1 Although the potential contribution of CETP to reverse cholesterol transport suggests an antiatherogenic mode of action, knowledge of the physiologic role of CETP in lipoprotein metabolism remains incomplete. The overall effect of CETP on atherogenesis may vary depending on both metabolic context and molecular variation in the CETP gene. 2 Investigations of associations between genetic variants in CETP and cardiovascular phenotypes are numerous, but often conflicting in their findings. The Taq1B polymorphism of the CETP gene has been associated with plasma levels of CETP and HDL cholesterol (HDL-C) and with the risk of coronary heart disease (CHD). 3,4 The Taq1B polymorphism has also been shown to serve as a marker of lipoprotein response to dietary intervention. 5,6 Other studies have demonstrated a link between the CETP I405V gene polymorphism and HDL-C, but not with response to diet. 7,8 Several other single nucleotide polymorphisms (SNPs) in the

show abstract

Section: Discussionmentioning

confidence: 99%

Haplotypes of the cholesteryl ester transfer protein gene predict lipid-modifying response to statin therapy

Winkelmann¹,

Hoffmann

Nauck

et al. 2003

Pharmacogenomics J

View full text Add to dashboard Cite

show abstract

“…A total of 9 population-based studies qualified for inclusion: 4 prospective studies: the Framingham Offspring Study (FOS), 20 the Physicians' Health Study (PHS), 21 the Northwick Park Heart Study (NPHS), 22 and the Reykjavik study; 23 and 5 cross-sectional studies: the European Atherosclerosis Research Study (EARS), 24 Etude Cas-Témoins de l'Infarctus du Myocarde (ECTIM), 15,25,26 the Oulu Project Elucidating Risk of Atherosclerosis (OPERA), 11,27 a study performed by Arca et al, 28 and one performed by Corella et al 29 Databases with individual patient data were obtained from all studies except for the FOS and the study performed by Corella et al 20,29 ; thus these 2 studies were not included. We identified 3 randomized, double-blind, placebo-controlled trials of pravastatin treatment wherein a subanalysis had been performed on the role of the TaqIB polymorphism: the Regression Growth Evaluation Statin Study (REGRESS), 7 the Cholesterol And Recurrent Events trial (CARE), 9 and the West of Scotland Coronary Prevention Study (WOSCOPS).…”

Section: Resultsmentioning

confidence: 99%

“…We investigated whether our pooled dataset provided any evidence for the published interactions between TaqIB genotype and sex, 11,12 smoking, 8,13 BMI, 13,14 and use of alcohol. 15 The present meta-analysis provides some evidence that interactions exist for both sex and smoking (Pϭ0.02 for each), such that the effect of TaqIB genotype on HDL-C levels was attenuated among men and among smokers.…”

Section: Effect Modification By Environmental Factorsmentioning

confidence: 99%

“…8,9 Such inconsistencies are often encountered among genetic association studies and can be due factors such as genetic admixture or lack of statistical power. 10 In this specific case, an alternative explanation may derive from proposed interactions with sex, 11,12 smoking, 8,13 body mass index (BMI), 13,14 and use of alcohol, 15 all modifiers of CETP action, HDL-C levels, and CAD risk. In view of our recent report about an interaction between CETP plasma levels and triglyceride levels, 16 we also explored a potential interaction between TaqIB genotype and triglyceride levels.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Cholesteryl Ester Transfer Protein TaqIB Variant, High-Density Lipoprotein Cholesterol Levels, Cardiovascular Risk, and Efficacy of Pravastatin Treatment

et al. 2005

View full text Add to dashboard Cite

Background-Several studies have reported that the cholesteryl ester transfer protein (CETP) TaqIB gene polymorphism is associated with HDL cholesterol (HDL-C) levels and the risk of coronary artery disease (CAD), but the results are inconsistent. In addition, an interaction has been implicated between this genetic variant and pravastatin treatment, but this has not been confirmed. Methods and Results-A meta-analysis was performed on individual patient data from 7 large, population-based studies (each Ͼ500 individuals) and 3 randomized, placebo-controlled, pravastatin trials. Linear and logistic regression models were used to assess the relation between TaqIB genotype and HDL-C levels and CAD risk. After adjustment for study, age, sex, smoking, body mass index (BMI), diabetes, LDL-C, use of alcohol, and prevalence of CAD, TaqIB genotype exhibited a highly significant association with HDL-C levels, such that B2B2 individuals had 0.11 mmol/L (0.10 to 0.12, PϽ0.0001) higher HDL-C levels than did B1B1 individuals. Second, after adjustment for study, sex, age, smoking, BMI, diabetes, systolic blood pressure, LDL-C, and use of alcohol, TaqIB genotype was significantly associated with the risk of CAD (odds ratioϭ0.78 [0.66 to 0.93]) in B2B2 individuals compared with B1B1 individuals (P for linearityϭ0.008). Additional adjustment for HDL-C levels rendered a loss of statistical significance (Pϭ0.4). Last, no pharmacogenetic interaction between TaqIB genotype and pravastatin treatment could be demonstrated. Conclusions-The CETP TaqIB variant is firmly associated with HDL-C plasma levels and as a result, with the risk of CAD. Importantly, this CETP variant does not influence the response to pravastatin therapy. (Circulation. 2005;111: 278-287.)

show abstract

“…The measurements of plasma triglyceride concentrations and very-low-density lipoprotein (VLDL), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels have been described in detail elsewhere (25). All the subjects volunteered for the study, which was approved by the Ethical Committee of the University of Oulu.…”

Section: Subjectsmentioning

confidence: 99%

Sequencing analysis of the ghrelin receptor (growth hormone secretagogue receptor type 1a) gene

Vartiainen

Poykko²,

Raisanen³

et al. 2004

European Journal of Endocrinology

View full text Add to dashboard Cite

Objectives and design: Ghrelin is a novel 28 amino acid peptide which is reported to have several endocrine and non-endocrine actions. It possesses strong growth hormone (GH)-releasing activity, which is mediated via the GH secretagogue receptor type 1a (GHS-R1a). We hypothesised that there might be functional sequential variations in the GHS-R1a gene affecting phenotypes linked to the GH/insulin-like growth factor-I (IGF-I)-axis. Methods: To test our hypothesis we chose patients from our OPERA (Oulu Project Elucidating Risk of Atherosclerosis) study with low (n ¼ 96) and high (n ¼ 96) IGF-I levels, sequenced their GHS-R1a gene exons and performed association studies. Results: We found five single-nucleotide polymorphisms (SNPs) which did not change the amino acid sequence. We were unable to detect associations between the SNPs and the IGF-I plasma concentrations, but instead we showed that SNP 171C . T was associated with the values of the area under the insulin curve (AUCIN) in an oral glucose tolerance test and with IGF-binding protein-1 (IGFBP-1) concentrations (P , 0.05). SNP 477G . A was associated with the low density lipoprotein and very low density lipoprotein cholesterol plasma levels and AUCIN values (P , 0.05). Conclusions: This study was the first genomic screening of the GHS-R1a gene in a population. It suggests that genetic variations in the GHS-R1a gene are not the main regulators of IGF-I levels. However, the variants may be associated with IGFBP-1 concentrations and insulin metabolism.

show abstract

Sex difference in the regulation of plasma high density lipoprotein cholesterol by genetic and environmental factors

Cited by 85 publications

References 28 publications

Haplotypes of the cholesteryl ester transfer protein gene predict lipid-modifying response to statin therapy

Haplotypes of the cholesteryl ester transfer protein gene predict lipid-modifying response to statin therapy

Cholesteryl Ester Transfer Protein TaqIB Variant, High-Density Lipoprotein Cholesterol Levels, Cardiovascular Risk, and Efficacy of Pravastatin Treatment

Sequencing analysis of the ghrelin receptor (growth hormone secretagogue receptor type 1a) gene

Contact Info

Product

Resources

About