I405V and TaqIB polymorphisms of the cholesteryl ester transfer protein and their relation to serum lipid and lipoprotein levels in a Turkish population

Cholesteryl ester transfer protein (CETP) plays a central role in high‐density lipoprotein (HDL) metabolism. Genetic polymorphisms of the CETP gene can influence levels of serum lipoproteins. It has been reported that mean HDL‐cholesterol (HDL‐C) concentrations are low in Turkish population. Thus, we investigated the frequencies of the common I405V and TaqIB polymorphisms of the CETP gene and their relation to serum lipid and lipoprotein levels in a Turkish population. The variant allele frequencies of I405V and TaqIB polymorphisms of the CETP gene were found to be 0.38 and 0.46, respectively and similar to some of the European populations. Subjects for the VV genotype of I405V polymorphism had higher HDL‐C levels than did II subjects. The covariance analysis showed that gender and triglyceride (TG) levels have an effect on the association of HDL‐C and I405V polymorphism. In conclusion, our results indicate that I405V polymorphism may affect the HDL‐C levels in Turkish population. The association of this polymorphism and HDL‐C levels could be modified by other factors, such as gender and TG levels. Copyright © 2009 John Wiley & Sons, Ltd.     

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

Association between high density lipoprotein (HDL) cholesterol concentration and restriction fragment length polymorphisms at the cholesteryl ester transfer protein (CETP) gene locus was studied in a random population-based cohort of 526 Caucasian subjects (259 men, mean age 50.9 years, and 267 women, mean age 51.8 years). HDL cholesterol concentration was adjusted for age, body mass index, alcohol consumption, smoking and plasma triglyceride and low density lipoprotein cholesterol levels. In females, the HDL cholesterol levels were associated withTagIB polymorphism (1.46 mmol/1 in the B1B1 genotype, 1.56 mmol/l in B 1B2 and 1.72 mmol/1 in B2B2,P = 0.0001 for the trend). In contrast, this was not observed in men (1.24, 1.20, 1.27 mmol/l, NS). The association was seen even in women who were current smokers (1.41, 1.56, 1.75 mmol/l,n = 72,P = 0.007), but not in male smokers (1.26, 1.19, 1.14 mmol/l,n = 102, NS). In male non-smokers the association was weak (1.22, 1.20, 1.32 mmol/l,n = 157,P = 0.05). In postmenopausal women not receiving hormone replacement therapy (n = 108), the association continued to be present, although weaker (1.50, 1.58, 1.70 mmol/l,P = 0.06). CETP activity (n = 101) tended to be lower in subjects with the 132132 genotype. In conclusion, a clear-cut sex difference was observed in the genotype effect on plasma HDL cholesterol levels. The slight attenuation of the gene dosage effect after menopause suggests that the gender difference may be, at least in part, due to sex hormones. A genetic subgroup (men with the 132132 genotype) particularly susceptible to the HDL cholesterol decreasing effect of smoking could be demonstrated.Part of this work was presented at the 67th Scientific Sessions of the American Heart Association, Dallas, Texas, USA, 14–17 November, 1994     

Genetic variations of cholesterol ester transfer protein gene in Koreans.

An absence of cholesterol ester transfer protein (CETP, protein; CETP, gene) results in an increase of the apolipoprotein AI levels and a decrease in the low density lipoprotein (LDL) levels. Thus, the CETP polymorphism is important in the assessment of risk of atherosclerosis. This study was conducted to elucidate the genotype distributions of the CETP polymorphism and association with plasma lipid levels in Koreans. The genotypes of the TaqI A and B polymorphic loci were associated with plasma triglyceride levels in the control and coronary artery disease (CAD) groups. There was linkage disequilibrium between TaqI A and B loci in the control group (chi2 = 5.58, p < 0.05). Association studies of the CETP polymorphism have been carried out mainly with Caucasian populations; however, the results have not been consistent among different populations. A possible explanation for this diversity among populations may be differences in genetic backgrounds, which may be more important than environmental factors. We discuss the reasons for the incompatibility of the CETP polymorphism among populations.     

Polymorphisms in ABCG5 and ABCG8 transporters and plasma cholesterol levels

ABCG5 and ABCG8 transporters play an important role in the absorption and excretion of sterols. Missence polymorphisms (Gln604Glu in the ABCG5 and Asp19His, Tyr54Cys, Thr400Lys, and Ala632Val in the ABCG8) in these genes have been described. In 131 males and 154 females whose dietary composition markedly changed and lipid parameters decreased over an 8-year follow-up study (total cholesterol decreased from 6.21+/-1.31 mmol/l in 1988 to 5.43+/-1.06 mmol/l in 1996), these polymorphisms were investigated using PCR. Plasma lipid levels and changes in plasma lipid levels were independent of the Gln604Glu polymorphism in ABCG5 and Asp19His and the Ala632Val polymorphisms in ABCG8. The Tyr54Cys polymorphism influenced the degree of reduction in total plasma cholesterol (delta -0.49 mmol/l in Tyr54 homozygotes vs. delta +0.12 mmol/l in Cys54 homozygotes, p<0.04) and LDL-cholesterol (delta -0.57 mmol/l in Tyr54 homozygotes vs. delta +0.04 mmol/l in Cys54 homozygotes, p<0.03) levels between 1988 and 1996 in females, but not in males. Male Thr400 homozygotes exhibited a greater decrease in total cholesterol (delta -0.90 mmol/l vs. delta -0.30 mmol/l, p<0.02) and LDL-cholesterol (delta -0.62 mmol/l vs. delta -0.19 mmol/l, p<0.04) than Lys400 carriers. No such association was observed in females. We conclude that Tyr54Cys and Thr400Lys variations in the ABCG8 gene may play a role in the genetic determination of plasma cholesterol levels and could possibly influence the gender-specific response of plasma cholesterol levels after dietary changes. These polymorphisms are of potential interest as genetic variants that may influence the lipid profile.     

Association of cholesteryl ester transfer protein −629C > A polymorphism with high‐density lipoprotein cholesterol levels in coronary artery disease patients

In Turkish population, plasma HDL‐C levels were found to be lower than in any other country and it is suggested that this is associated with genetic origin. The cholesteryl ester transfer protein (CETP) ?629C > A polymorphism is associated with lower plasma CETP concentration, with increased HDL‐C level. In the present study, the frequency of ?629C > A polymorphism in patients with coronary artery disease (CAD) was investigated and the effect of genotype on HDL‐C was evaluated in a Turkish population. For this aim CETP ?629C > A polymorphism was studied in angiographically documented CAD patients and healthy controls. There was no statistical significance in the distribution of genotypes between patients and controls. Although A allele carriers with CAD had significantly lower HDL‐C levels than controls, plasma lipid levels showed no difference according to the genotypes. Adjustment by a logistic regression model predicting CAD status through HDL‐C and including some risk factors as covariate indicated that the HDL‐C doesn't have a significant association with CAD risk in CA and AA genotype carriers. Smoking, gender and hypertension were the common predictors for the HDL‐C levels in CA and AA carriers. Although HDL‐C appeared to be the only significant predictor of CAD in our study groups, the contribution of CETP ?629C > A polymorphism to the alterations in HDL‐C level appears to be weak to mention a protective effect of this polymorphism for CAD. In conclusion, the findings of the present study indicate that the CETP ?629C > A polymorphism is not among the determinants of the coronary artery disease in Turks. Copyright © 2009 John Wiley & Sons, Ltd.     

The ability of plasma to stimulate fibroblast cholesterol efflux is associated with the -629C-->A cholesteryl ester transfer protein promoter polymorphism: role of lecithin: cholesterol acyltransferase activity

A recent population-based study showed that cholesteryl ester transfer protein (CETP) gene variations, which relate to lower plasma CETP, may predict increased cardiovascular risk, in spite of higher HDL cholesterol. Among other functions, CETP activity contributes to cellular cholesterol efflux, an early step in the anti-atherogenic reverse cholesterol transport (RCT) process. We hypothesized that cellular cholesterol efflux stimulating capacity of plasma could be associated with CETP gene variation. In this study, we tested the extent to which the ability of plasma to promote cholesterol efflux from cultured human fibroblasts is associated with CETP gene variation. In 223 men, the -629C-->A CETP promoter polymorphism, plasma lipids, CETP mass, cholesteryl ester transfer (CET), lecithin:cholesterol acyltransferase (LCAT) activity and the ability of plasma to promote cholesterol efflux from human skin fibroblasts, obtained from a single normolipidemic donor, were determined. In -629CC homozygotes (n=52), cholesterol efflux, plasma CETP mass, CET and LCAT activity were higher, whereas HDL cholesterol was lower compared to -629 AA homozygotes (n=62) and -629CA+AA carriers (n=171) (P<0.05 to P<0.001). Univariate correlation analysis showed that cellular cholesterol efflux was related to CETP genotype (P=0.04), plasma CET (P<0.05), LCAT activity (P<0.001) and apo A-I (P<0.05). Multiple linear regression analysis confirmed the independent association of cellular cholesterol efflux to plasma with CETP genotype. In conclusion, an association of cellular cholesterol efflux with the -629C-->A CETP polymorphism, possibly also involving LCAT activity, could provide a mechanism explaining why CETP gene variation, which relates to lower plasma CETP, does not confer diminished cardiovascular risk.     

Role of CETP inhibitors in the treatment of dyslipidemia

PURPOSE OF REVIEW: This review summarizes novel human data on cholesteryl ester-transfer protein (CETP) and atherosclerosis and the possible use of CETP inhibitors in the treatment of dyslipidemia. In addition, it will underline that therapeutic targeting of the high-density lipoprotein (HDL) metabolism entails more than simply observing changes in cholesterol levels of this lipoprotein. RECENT FINDINGS: Two pharmacological small-molecule inhibitors of CETP, JTT-705 and torcetrapib, have recently been shown to effectively raise HDL cholesterol in humans without serious side effects when either used as a monotherapy or combined with statins that lower low-density lipoprotein cholesterol. Importantly, prospective data from the Epic-Norfolk study furthermore indicate that elevated CETP concentration in conjunction with elevated triglyceride levels are associated with increased odds for cardiovascular events. Data from the Diabetic Atherosclerosis Intervention Study furthermore show that elevated CETP concentration is associated with increased progression of coronary atherosclerosis in patients with type 2 diabetes who use fenofibrate. SUMMARY: Long-term studies will have to show whether CETP inhibition decreases the risk of atherosclerotic disease in dyslipidemic patients. Increased CETP activity might be detrimental under hypertriglyceridemic conditions which is of importance when considering that a large proportion of patients at increased risk from coronary artery disease exhibit elevated triglyceride levels. Studies into the effects of CETP inhibition in hypertriglyceridemic patients therefore seem warranted. Awaiting the first data on the effect of CETP inhibition on surrogate endpoints for atherosclerosis, this review furthermore outlines that the complexity of HDL metabolism will necessitate a wide variety of studies on many aspects of this intriguing lipoprotein.     

Apolipoprotein composition of HDL in cholesteryl ester transfer protein deficiency

Our purpose was to compare HDL subpopulations, as determined by nondenaturing two-dimensional gel electrophoresis followed by immunoblotting for apolipoprotein A-I (apoA-I), apoA-II, apoA-IV, apoCs, and apoE in heterozygous, compound heterozygous, and homozygous subjects for cholesteryl ester transfer protein (CETP) deficiency and controls. Heterozygotes, compound heterozygotes, and homozygotes had CETP masses that were 30, 63, and more than 90% lower and HDL-cholesterol values that were 64, 168, and 203% higher than those in controls, respectively. Heterozygotes had approximately 50% lower pre-beta-1 and more than 2-fold higher levels of alpha-1 and pre-alpha-1 particles than controls. Three of the five heterozygotes' alpha-1 particles also contained apoA-II, which was not seen in controls. Compound heterozygotes and homozygotes had very large particles not observed in controls and heterozygotes. These particles contained apoA-I, apoA-II, apoCs, and apoE. However, these subjects did not have decreased pre-beta-1 levels. Our data indicate that CETP deficiency results in the formation of very large HDL particles containing all of the major HDL apolipoproteins except for apoA-IV. We hypothesize that the HDL subpopulation profile of heterozygous CETP-deficient patients, especially those with high levels of alpha-1 containing apoA-I but no apoA-II, represent an improved anti-atherogenic state, although this might not be the case for compound heterozygotes and homozygotes with very large, undifferentiated HDL particles.     

The CETP I405V polymorphism is associated with an increased risk of Alzheimer's disease

The cholesteryl ester transfer protein (CETP) gene plays an essential role in regulating cholesterol homeostasis and is a candidate susceptibility gene for late-onset Alzheimer's disease (AD). Recent finding suggests that the CETP I405V polymorphism (rs5882) is associated with a slower rate of memory decline and a lower risk of incident dementia. Using data from two ongoing epidemiologic clinical-pathologic cohort studies of aging and dementia in the United States, the Religious Order Study and the Memory and Aging Project, we evaluated the association of the CETP I405V polymorphism (rs5882) with cognitive decline and risk of incident AD in more than 1300 participants of European ancestry. Our results suggest that the CETP I405V polymorphism was associated with a faster rather than a slower rate of decline in cognition over time, and an increased risk of incident AD. This finding is consistent with data showing that the CETP I405V is associated with increased neuritic plaque density at autopsy.     

Genetic factors affecting HDL levels, structure, metabolism and function

PURPOSE OF REVIEW: HDL is a recognized negative risk factor for the cardiovascular diseases. Establishing the genetic determinants of HDL concentration and functions would add to the prediction of cardiovascular risk and point to the biochemical mechanisms underlying this risk. The present review focuses on various approaches to establish genetic determinants of the HDL concentration, structure and function. RECENT FINDINGS: While many genes contribute to the HDL concentration and collectively account for half of the variability, polymorphism of individual candidate genes contributes little. There are strong interactions between environmental and genetic influences. Recent findings have confirmed that APOA1 and ABCA1 exert the strongest influence on HDL concentrations and risk of atherosclerosis. CETP and lipases also affect the HDL concentration and functionality, but their connection to the atherosclerosis risk is conditional on the interaction between environmental and genetic factors. SUMMARY: Analysis of genetic determinants of HDL-cholesterol in patients with specific disease states or in response to the environmental condition may be a more accurate way to assess variations in HDL concentration. This may result in defining the rules of interaction between genetic and environmental factors and lead to understanding the mechanisms responsible for the variations in HDL concentration and functionality.     

Cardiovascular risk in rheumatoid arthritis versus osteoarthritis: acute phase response related decreased insulin sensitivity and high-density lipoprotein cholesterol as well as clustering of metabolic syndrome features in rheumatoid arthritis

Rheumatoid arthritis (RA) patients experience a markedly increased frequency of cardiovascular disease. We evaluated cardiovascular risk profiles in 79 RA patients and in 39 age-matched and sex-matched osteoarthritis (OA) patients. Laboratory tests comprised ultrasensitive C-reactive protein (CRP) and fasting lipids. Insulin sensitivity (IS) was determined by the Quantitative Insulin Sensitivity Check Index (QUICKI) in all OA patients and in 39 of the RA patients. Ten RA patients were on glucocorticoids. RA patients exercised more frequently than OA patients (χ² = 3.9, P < 0.05). Nine RA patients and one OA patient had diabetes (χ² = 4.5, P < 0.05). The median CRP, the mean QUICKI and the mean high-density lipoprotein (HDL) cholesterol were 9 mg/l (range, 0.5–395 mg/l), 0.344 (95% confidence interval [CI], 0.332–0.355) and 1.40 mmol/l (95% CI, 1.30–1.49 mmol/l) in RA patients, respectively, as compared with 2.7 mg/l (range, 0.3–15.9 mg/l), 0.369 (95% CI, 0.356–0.383) and 1.68 mmol/l (95% CI, 1.50–1.85 mmol/l) in OA patients. Each of these differences was significant (P < 0.05). After controlling for the CRP, the QUICKI was similar in RA and OA patients (P = 0.07), while the differences in HDL cholesterol were attenuated but still significant (P = 0.03). The CRP correlated with IS, while IS was associated with high HDL cholesterol and low triglycerides in RA patients and not in OA patients. A high CRP (≥ 8 mg/l) was associated with hypertension (χ² = 7.4, P < 0.05) in RA patients. RA glucocorticoid and nonglucocorticoid users did not differ in IS and lipids (P > 0.05). Excess cardiovascular risk in RA patients as compared with OA patients includes the presence of decreased IS and HDL cholesterol in RA patients. The latter is only partially attributable to the acute phase response. The CRP, IS, HDL cholesterol, triglycerides and hypertension are inter-related in RA patients, whereas none of these relationships were found in OA patients.     

Antisense oligonucleotide inhibition of cholesteryl ester transfer protein enhances RCT in hyperlipidemic,CETP transgenic,LDLr-/- mice

Due to their ability to promote positive effects across all of the lipoprotein classes, cholesteryl ester transfer protein (CETP) inhibitors are currently being developed as therapeutic agents for cardiovascular disease. In these studies, we compared an antisense oligonucleotide (ASO) inhibitor of CETP to the CETP small molecule inhibitor anacetrapib. In hyperlipidemic CETP transgenic (tg) mice, both drugs provided comparable reductions in total plasma cholesterol, decreases in CETP activity, and increases in HDL cholesterol. However, only mice treated with the antisense inhibitor showed an enhanced effect on macrophage reverse cholesterol transport, presumably due to differences in HDL apolipoprotein composition and decreases in plasma triglyceride. Additionally, the ASO-mediated reductions in CETP mRNA were associated with less accumulation of aortic cholesterol. These preliminary findings suggest that CETP ASOs may represent an alternative means to inhibit that target and to support their continued development as a treatment for cardiovascular disease in man.     

Effects of cholesterol ester transfer protein Taq1B gene polymorphism on serum lipoprotein levels in Turkish coronary artery disease patients

To evaluate the effect of cholesterol ester transfer protein (CETP) Taq1B gene polymorphism on serum lipid profile in Turkish coronary artery disease (CAD) patients, we investigated Taq1B gene polymorphism of CETP and serum lipid levels in 111 controls and in 173 CAD patients with myocardial infarction. There were no significant differences in the allele distribution at this polymorphic locus between the population sample and patients with coronary artery disease with myocardial infarction. To detect the association between the Taq1B RFLP and serum lipid levels, we determined the serum concentrations of total cholesterol, triglycerides and high density lipoprotein cholesterol (HDL-C) in the subjects studied and correlated the results to the Taq1B RFLP. Patients with Taq B1B1 genotypes had lower HDL-C levels than patients with B2B2 genotype (p = 0.003). Also in control subjects with Taq B1B1 genotype, lower HDL-C levels (p = 0.05) and higher triglyceride levels (p = 0.017) and body mass index (p = 0.05) were observed compared with control subjects with the B1B2 genotype. It was observed that in our population the distribution of CETP Taq1B genotypes is similar to other populations (except Greeks). The present study demonstrates that CETP Taq1B gene polymorphism may be responsible for low HDL cholesterol levels in patients with CAD and in healthy controls in Turkey.     

Association of cholesteryl ester transfer protein (TaqIB) and apolipoprotein E (HhaI) gene variants with obesity

Background The pathophysiology of obesity is known to be influenced by alterations in lipid levels. We aimed to evaluate association of cholesteryl ester transfer protein (CETP) and apolipoprotein (APO) E gene variants with asymptomatic obesity. Methods A total of 437 subjects, 159 asymptomatic obese (BMI = 29.29 +/- 3.76) and 278 non-obese (BMI = 23.38 +/- 1.71) individuals, were included in this case-control study. Lipid levels were estimated using standard protocols. Analysis of CETP (TaqIB) and APOE (HhaI) gene polymorphisms was done using PCR-RFLP. Results We found significant difference in blood pressure (systolic, P < 0.0001 and diastolic, P < 0.0001), total cholesterol (P < 0.0001), LDL-cholesterol (P < 0.0001), and HDL-cholesterol (P < 0.0001) in obese as compared to non-obese group. Homozygous APO E4E4 genotype was only observed in 5.7% of obese individuals and none in non-obese group. APO E4 allele carriers were also susceptible for obesity (P = 0.016, OR = 1.73; 95% CI = 1.12-2.68) than non-carriers. Higher blood pressure (Systolic, P = 0.001 and Diastolic, P = 0.004) and triglyceride levels (P = 0.029) were observed in obese subjects with APO E4 allele than individuals without APO E4. However, CETP B1 variant allele carriers did not show alteration in blood pressure and lipid profile in asymptomatic obese subjects. Conclusions APO E4 genotype and allele were found to be associated with asymptomatic obesity, whereas CETP Taq1B polymorphism showed no such association in North Indian subjects.     

Inverse association of plasma level of high-density lipoprotein cholesterol with intracerebral hemorrhage

This study aimed to investigate whether plasma levels of HDL cholesterol (HDL-C) were associated with the risk of intracerebral hemorrhage (ICH). Plasma HDL-C was determined via enzymatic methods, and ICH was ascertained via medical history, physical examination, and brain imaging (computed tomography or magnetic resonance imaging). The multivariable logistic regression model was used to calculate the odds ratios (OR) and 95% confidence intervals (CI) of ICH according to levels of plasma cholesterol. A total of 170 patients with ICH were identified from 6,046 participants. After adjustment for conventional cardiovascular risk factors, the OR was 2.06 (95% CI, 1.25-3.12; P < 0.01) for participants in the first tertile of HDL-C levels (<1.38 mmol/l) and 1.13 (95% CI, 0.72-1.78; P = 0.59) for participants in the second tertile (1.38-1.64 mmol/l), compared with participants in the third tertile (∩≥1.65 mmol/l). Subgroup analysis indicated that the detrimental effects of HDL-C were more significant in men and lean participants than in their corresponding controls, independent of hypertension. The results presented herein indicate that low plasma HDL-C (<1.38 mmol/l) may be associated with risk of ICH.     

Alcohol consumption and its relation to cardiovascular risk factors in British women.

OBJECTIVE--To examine the relation between alcohol consumption and risk factors for coronary heart disease in women. DESIGN--Cross sectional study of a stratified random sample of the population grouped into five categories of habitual alcohol consumption. SETTING--People registered with general practitioners at two large health centres in east Bristol, England. SUBJECTS--1048 women aged 25-69 years. MAIN OUTCOME MEASURES--Fasting plasma concentrations of insulin, total cholesterol, total triglycerides, and high density lipoprotein cholesterol, including its subfractions HDL2 and HDL3, and body mass index. RESULTS--Compared with non-drinkers women consuming a moderate amount of alcohol (1-20 g/day) had lower plasma concentrations of triglycerides, by 0.19 mmol/l (95% confidence interval 0.07 to 0.35); cholesterol, by 0.4 mmol/l (0.19 to 0.61); and insulin, by 1.4 mU/l (0.43 to 1.97) and a lower body mass index, by 1.2 kg/m2 (0.43 to 1.97). They also had higher concentrations of high density lipoprotein cholesterol, by 0.09 mmol/l (0.03 to 0.15); HDL2 cholesterol by 0.05 mmol/l (-0.02 to 0.10) and HDL3 cholesterol, by 0.06 mmol/l (0.06 to 0.11). All these were independent of body mass index, smoking habits, and taking oral contraceptives. CONCLUSIONS--Moderate alcohol consumption is associated with lower levels of cardiovascular risk factors in women. Insulin may have a central role.     

Influence of insulin sensitivity and the TaqIB cholesteryl ester transfer protein gene polymorphism on plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities and their response to hyperinsulinemia in non-diabetic men.

Lecithin:cholesteryl acyl transferase (LCAT), cholesteryl ester transfer protein (CETP), phospholipid transfer protein (PLTP), and lipoprotein lipases are involved in high density lipoprotein (HDL) metabolism. We evaluated the influence of insulin sensitivity and of the TaqIB CETP gene polymorphism (B1B2) on plasma LCAT, CETP, and PLTP activities (measured with exogenous substrates) and their responses to hyperinsulinemia. Thirty-two non-diabetic men without hyperlipidemia were divided in quartiles of high (Q(1)) to low (Q(4)) insulin sensitivity. Plasma total cholesterol, very low + low density lipoprotein cholesterol, triglycerides, and apolipoprotein (apo) B were higher in Q(4) compared to Q(1) (P < 0.05 for all), whereas HDL cholesterol and apoA-I were lowest in Q(4) (P < 0.05 for both). Plasma LCAT activity was higher in Q(4) than in Q(1) (P < 0. 05) and PLTP activity was higher in Q(4) than in Q(2) (P < 0.05). Insulin sensitivity did not influence plasma CETP activity. Postheparin plasma lipoprotein lipase activity was highest and hepatic lipase activity was lowest in Q(1). Insulin infusion decreased PLTP activity (P < 0.05), irrespective of the degree of insulin sensitivity. The CETP genotype exerted no consistent effects on baseline plasma lipoproteins and LCAT, CETP, and PLTP activities. The decrease in plasma PLTP activity after insulin was larger in B1B1 than in B2B2 homozygotes (P < 0.05). These data suggest that insulin sensitivity influences plasma LCAT, PLTP, lipoprotein lipase, and hepatic lipase activities in men. As PLTP, LCAT, and hepatic lipase may enhance reverse cholesterol transport, it is tempting to speculate that high levels of these factors in association with insulin resistance could be involved in an antiatherogenic mechanism. A possible relationship between the CETP genotype and PLTP lowering by insulin warrants further study.     

Association of Two CETP Polymorphisms With HDL Levels in the Chinese Obese Population

The association of two cholesterol ester transfer protein (CETP) polymorphisms, D442G and TAQIB (B1→B2), with high‐density lipoprotein (HDL) levels in 932 Chinese obese individuals (BMI ≥ 27) was investigated in comparison with normal controls (BMI ≤ 24). Independent association was demonstrated for TAQIB minor allele B2 and CETP442 minor allele G with elevated HDL levels. The CETP D442G polymorphism was associated with a much greater increase in HDL levels in subjects with BMI exceeding 27 kg/m² (+5.42 mg/dl, P = 0.0007) compared to normal controls (+1.97 mg/dl, P = 0.275), and the increase in HDL reached the highest level among subjects with BMI exceeding 30 kg/m² (+6.80 mg/dl, P = 0.016). TAQIB showed significant association with HDL levels only in normal BMI subgroup (P = 0.0017). TAQIB significantly interacted with serum triglyceride (TG) on modulating HDL levels (P = 0.027). The TAQIB–TG interaction effect remained marginally significant after controlling for BMI (P = 0.057). We conclude that D442G polymorphism is associated with more HDL elevation in obesity. TAQIB interacts with serum TG on modulating HDL levels, and the interaction is partly independent of BMI.