TaqIB Polymorphism Research Articles

Increased Coronary Heart Disease Risk Determined by High High-Density Lipoprotein Cholesterol and C-Reactive Protein: Modulation by Variation in the CETP Gene

Epidemiological evidence strongly favors the notion that the risk of cardiovascular disease (CVD) is inversely related to the plasma high-density lipoprotein (HDL) cholesterol concentration.1 Low HDL cholesterol is still predictive of high CVD risk in subjects with low LDL cholesterol,2 as well as during statin treatment.3 These observational data and other studies, which show that HDL particles contain a large number of antioxidative, antiinflammatory, and antiproliferative proteins, underlie the generally held view that HDL particles have atheroprotective properties.1–5 However, evidence is accumulating supporting the concept that high HDL cholesterol levels do not always predict reduced CVD risk. The Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) trial and the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk case-control study revealed that (recurrent) CVD risk is not decreased in subjects with the highest HDL cholesterol and the greatest mean HDL particle size.6 More recently, a high HDL cholesterol, high C-reactive protein (CRP) subgroup of individuals at increased risk for a first cardiovascular event was identified in the community-dwelling Prevention of Renal and Vascular End-Stage Disease (PREVEND) cohort using the “outcome event mapping approach,” a graphical exploratory data analysis tool that has been originally developed by Corsetti et al.7 Applying this analytic method to the Thrombogenic Factors and Recurrent Coronary Events (THROMBO) postinfarction cohort, the presence of a subgroup …

HDL Cholesterol Levels in Children with Mild Hypercholesterolemia: Effect of Consuming Skim Milk Enriched with Olive Oil and Modulation by the TAQ 1B Polymorphism in the CETP Gene

Background: This study aimed to examine the changes in serum lipids in children with mild hypercholesterolemia after the use of skim milk or olive-oil-enriched skim milk in their diet and the modulation of lipid levels by the Taq 1B polymorphism in the cholesteryl-ester transfer protein gene. Methods: Thirty-six prepubertal children with mild hypercholesterolemia were randomly assigned in a crossover design into 2 groups of 16 and 20 individuals. Both groups received, in sequential inverse order, the 2 types of milk for 2 periods of 6 weeks. Results: Carriers of at least 1 B2 allele had an adjusted basal HDL cholesterol level significantly higher than children with the B1B1 genotype (1.291 mmol/l, 95% CI: 1.184–1.397, vs. 1.082 mmol/l, 95% CI: 0.931–1.233; p = 0.027). In contrast, there were no significant differences in the adjusted basal levels of apolipoprotein A-I (B2 carriers: 1.292 g/l, 95% CI: 1.218–1.367; B1B1 genotype: 1.215 g/l, 95% CI: 1.109–1.320; p = 0.223). The intake of olive-oil-enriched skim milk caused significant increases in HDL cholesterol and apolipoprotein A-I, both in B2 (0.089 mmol/l, 95% CI: 0.032–0.146, p = 0.005; 0.55 g/l, 95% CI: 0.012–0.098; p = 0.018) and in B1B1 carriers (0.179 mmol/l, 95% CI: 0.096–0.262; p < 0.001; and 0.095 g/l, 95% CI: 0.032–0.157; p = 0.003). This increase in HDL cholesterol was significantly higher in the B1B1 group (p = 0.049). Conclusion: The consumption of skim milk enriched with olive oil increases the HDL cholesterol and apolipoprotein A-I levels in children with hypercholesterolemia, this effect being more intense in carriers of the B1B1 genotype.

TaqIB polymorphism in the CETP gene modulates the impact of HC/LF diet on the HDL profile in healthy Chinese young adults

The aim of this study was to investigate the interactions of genetic variants in the genes of cholesterol ester transfer protein ( CETP) and low-density lipoprotein receptor ( LDLR) with high carbohydrate and low fat (HC/LF) diet on lipid profiles in a young and healthy Chinese Han population. Fifty-six healthy subjects (22.89±1.80 years) were given washout diets of 31% fat and 54% carbohydrate for 7 days, followed by HC/LF diets of 15% fat and 70% carbohydrate for 6 days, with no total energy restriction. Serum lipid profiles at baseline, after washout and following HC/LF diets, as well as CETP and LDLR polymorphisms were analyzed. Carriers of B2 allele of CETP TaqIB polymorphism had significantly higher levels of high density lipoprotein cholesterol (HDL-C) and apo A-I in the whole study population after the diet intervention. Notably, males with CETP TaqIB B1B1 experienced significantly increased HDL-C and apo A-I after HC/LF diet. Regarding the LDLR Pvu II polymorphism, both P1P1 subjects and P2 carriers experienced decreased total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) levels after HC/LF diet with no statistically significant differences between the genotypes. Our results demonstrate that the elevated HDL-C levels after HC/LF diet in healthy Chinese Han youth are associated with CETP TaqI B2 allele while males with B1B1 genotype are more susceptible to the influence of HC/LF diet on their HDL-C levels. The decreased TC and LDL-C levels after HC/LF diet are not associated with LDLR Pvu II polymorphism.

Cholesteryl Ester Transfer Protein Gene Polymorphisms and Longevity Syndrome

Purpose:High levels of high density lipoprotein (HDL) cholesterol are associated with a decreased risk of coronary heart disease (CHD). Subjects with high levels of HDL cholesterol (>70 mg/dl; 1.79 mmol/l) as well as high levels of low density lipoprotein (LDL) cholesterol, could represent a group with longevity syndrome (LS). Since HDL particles are influenced by cholesteryl ester transfer protein (CETP) activity, it is worth studying the CETP polymorphism. The aim of the study was to detect whether 2 genetic variants of the CETP are associated with the LS.Subjects and Methods:The study population consisted of 136 unrelated men and women with no personal and family history of CHD; 69 met the criteria for LS and 67 did not meet these criteria and had “normal” HDL cholesterol (>40 and <70 mg/dl; >1.03 and <1.79 mmol/l). All patients were genotyped for the TaqIB and I405V polymorphisms.Results:The B2 allele frequency of TaqIB polymorphism was higher in the LS in comparison with the non-LS group (p=0.03) whereas B1 allele frequency was higher in the non-LS group (p=0.03).Conclusions:Gene polymorphisms could help decide whether individuals who have increased levels of both LDL cholesterol and HDL cholesterol require treatment. Some of the prerequisites could include that subjects with LS should not only have very high levels of HDL cholesterol but also favorable gene polymorphisms. However, further investigations with a larger sample and including other gene polymorphisms, are needed.

Influence of menopause and cholesteryl ester transfer protein (CETP) TaqIB polymorphism on lipid profile and HDL subpopulations distribution in women with and without type 2 diabetes

The common TaqIB variant in the gene coding for cholesteryl ester transfer protein (CETP), a key enzyme in reverse cholesterol transport, has been associated with higher HDL-C levels and with a more atheroprotective HDL subpopulations profile. Similar information are lacking in women with diabetes. The effect of menopause and the CETP polymorphism on lipid, lipoprotein profile, as well as on apoA-I-containing HDL subclasses distribution, as determined by two-dimensional gel electrophoresis, was examined in a group of women with and without type 2 diabetes.Diabetic women showed a less atheroprotective lipid and HDL subpopulations profile, with lower levels of the large α-1 (P=0.006), α-2 (P=0.005), and preα-1 (P=0.02), and higher concentration of the small α-3 HDL particles (P=0.02) as compared to controls, independently from menopause, HDL-C and triglycerides concentrations.CETP TaqIB genotype distribution was in the Hardy–Weinberg equilibrium and comparable in the two groups, but the effect of CETP polymorphism was limited to diabetic women. In this group, the CETP variant showed significant interactions with HOMAIR (P<0.001), BMI (P<0.001), and triglycerides (P<0.00001), with significantly higher HDL-C levels and a more protective HDL subpopulations profile in B2 allele carriers with lower HOMAIR, BMI or triglycerides levels.At multivariate analysis, CETP polymorphism, apoA-I, triglycerides and BMI were independent determinants of HDL-C concentration in diabetic women; apo-A-I, triglycerides, age and creatinine in controls.Type 2 diabetes is associated with a more atherogenic lipid profile; the CETP TaqIB variant may partly prevent these modifications in diabetic women with a milder degree of insulin resistance and its related disorders.

Association of Taq 1B CETP polymorphism with insulin and HOMA levels in the population of the Canary Islands

Background and aims Cholesteryl ester transfer protein (CETP) is an enzyme with a key role in lipoprotein metabolism. A common genetic polymorphism, the Taq 1B, influences CETP activity and HDL-cholesterol levels, with individual homozygotes for the B1 allele exhibiting higher enzyme activity and lower HDL-cholesterol levels than carriers of at least one B2 allele. Our aim was to analyze the influence of Taq 1B CETP polymorphism on cardiovascular risk factors in a representative sample of adult subjects from Canary population. Methods and result A total of 518 adult subjects from the Canary Islands, enrolled in a nutritional survey (the ENCA study), were included. The Taq 1B polymorphism was analyzed by PCR–RFLP. Compared with individuals with at least one B2 allele, and after adjusting for age, sex, BMI, waist perimeter, smoking and alcohol intake, carriers of the B1B1 genotype showed lower HDL-cholesterol levels (geometric mean (95% CI): 46.6 (44.5–48.8) vs. 50.6 (49.1–52.9) mg/dl; P = 0.003); and higher insulin (geometric mean (95% CI): 11.1 (10.5–11.9) vs. 10.0 (9.5–10.5 μU/ml; P = 0.008) and HOMA levels (geometric mean (95% CI): 2.3 (2.1–2.5) vs. 2.1 (1.9–2.1); P = 0.009). In addition, the B1B1 genotype was more frequent in individuals who had low levels of HDL-cholesterol according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria (Odds Ratio (OR): 1.563; 95% CI: 1.04–2.34; P = 0.030), and in those included in the upper quartile of insulinemia (OR: 1.90; 95% CI: 1.20–3.03; P = 0.007) and HOMA (OR: 1.61; 95% CI: 1.02–2.57; P = 0.043). Conclusion The observed influence of Taq 1B polymorphism on insulin levels and HOMA highlights the possible role of CETP in the regulation of glucose homeostasis.

Sex-associated effect of CETP and LPL polymorphisms on postprandial lipids in familial hypercholesterolaemia

BackgroundThis study assessed the gender-specific influence of the cholesteryl ester transfer protein (TaqIB, I405V) and lipoprotein lipase (S447X) polymorphisms on the response to an oral fat tolerance test in heterozygotes for familial hypercholesterolaemia.MethodsWe selected and genotyped 80 men and postmenopausal women heterozygous for familial hypercholesterolaemia (main group) as well as 11 healthy control subjects. Patients were subgrouped based on their response to oral fat tolerance test. The oral fat tolerance test was defined as pathological when postprandial triglyceride concentration was higher than the highest triglyceride concentration observed in healthy subjects (220 mg/dl) at any time (2, 4, 6 or 8 h).ResultsIn the pathological subgroup, men had significantly higher incremental area under the curve after oral fat tolerance test than postmenopausal women. Furthermore, multivariate analysis revealed a gender association of TaqIB and I405V influence on postprandial lipaemia in this subgroup.ConclusionIn conclusion, it seems that gender and TaqIB polymorphism of the cholesteryl ester transfer protein gene were both associated with the distribution of triglyceride values after oral fat tolerance test, only in subjects with a pathological response to oral fat tolerance test. Specifically, men carrying the B2 allele of the TaqIB polymorphism showed a higher postprandial triglyceride peak and a delayed return to basal values compared with women carrying B2. However, further investigations in larger populations are required to replicate and confirm these findings.

The effect of a novel intergenic polymorphism (rs11774572) on HDL-cholesterol concentrations depends on TaqIB polymorphism in the cholesterol ester transfer protein gene

Background and aimsSeveral genes have been shown to individually affect plasma lipoprotein metabolism in humans. Studies on gene–gene interactions could offer more insight into how genes affect lipid metabolism and may be useful in predicting lipid concentrations. We tested for gene–gene interactions between TaqIB SNP in the cholesterol ester transfer protein (CETP) and three novel single nucleotide polymorphisms (SNPs), namely rs11774572, rs7819412 and rs6995374 for their effect on metabolic syndrome (MetS) components and related traits. Methods and resultsThe aforementioned SNPs were genotyped in 1002 subjects who participated in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. Lipids were measured by standard procedures and lipoprotein subfractions, by proton nuclear magnetic resonance spectroscopy. Polymorphism rs11774572 was significantly associated with MetS (P=0.020), mainly driven by the association of the C allele with lower HDL-C (P=0.043) and higher triglycerides (P=0.049) and insulin (P=0.040) concentrations than TT subjects. A significant interaction between SNPs rs11774572 and CETP-TaqIB SNPs was found for HDL-C concentrations (P=0.006) and for HDL (P=0.008) and LDL particle sizes (P=0.009), small LDL (P=0.004), and VLDL concentrations (P=0.021), in which TT homozygotes displayed higher HDL-C concentrations and for HDL and LDL particle sizes, and lower small LDL and VLDL concentrations than C carriers, if they were CETP B2 allele carriers (P values ranging from <0.001 to 0.001). ConclusionsThe rs11774572 polymorphism may play a role in the dyslipidemia that characterizes MetS. The interaction between rs11774572 and CETP-TaqIB SNPs on HDL-C concentrations provides some insights into the underlying mechanisms.

TAQIB and I405V polymorphisms of CETP are moderately associated with obesity risk in the Chinese adult population

Associations between the TAQIB and I405V polymorphisms and obesity risk were studied for a single locus as well as in combination. A total of 934 obese subjects and 924 normal controls were included in the study. TAQIB was associated with high-density lipoprotein (HDL) levels (P < 0.001), while I405V was associated with levels of low-density lipoprotein (P = 0.03) and total cholesterol (P = 0.007). Less common alleles of TAQIB and I405V were associated with decreased obesity risk and further drops in odds ratio (OR) were observed in carriers with rare homozygous alleles on both loci (OR = 0.659, P = 0.02). The TAQIB B2 allele was associated with reductions in both hip circumference (P = 0.034) and triceps skinfold thickness (TST) (P = 0.045), although this effect was completely abolished after controlling for HDL levels. The 405V variant was associated with reductions in hip circumference (P = 0.031), body fat composition (P = 0.039) and TST (P = 0.036); these effects were weakened (P < 0.1) after controlling for HDL levels. In conclusion, less common alleles of TAQIB and I405V appear to be modestly associated with obesity risk in an adult Chinese population. Adjustments for HDL levels completely (TAQIB) or partially (I405V) abolished the observed association.

Genetic determinants of plasma HDL-cholesterol levels in prepubertal children

Introduction Genetic determinants have been related to variation of high-density lipoprotein cholesterol (HDL-C) levels, but the extension of this association remains controversial. In our study, we analyzed the contribution of several polymorphisms on HDL-C-related genes to variation of plasma HDL-C in prepubertal children. Methods We studied 1269 (641 males and 628 females) 6–8 years old healthy children, who participated in a cross-sectional study examining cardiovascular risk factors in Spain. Common genetic variants in the apolipoprotein AI, apolipoprotein AII, cholesteryl ester transfer protein (CETP), hepatic lipase, ATP-binding cassette transporter A1, and paraoxonase genes were determined by PCR. Results CETP TaqI B2 carrier girls had significantly higher HDL-C levels than B1B1 girls. B2B2 boys had significantly higher ( p < 0.001) HDL-C than B1B1and B1B2 boys. In linear regression analysis, CETP TaqIB appears as the main predictor of HDL-C plasma levels, accounting for 4.5% and 1.8% of HDL-C variation in girls and boys respectively. Conclusions Our data showed that among the studied polymorphisms only the CETP TaqIB polymorphism contributes to the variation in HDL-C levels in prepubertal children, particularly in girls, but overall these polymorphisms explain a small part of the variation of HDL-C plasma levels at this age.

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.

TaqIB polymorphism in cholesterol ester transfer protein (CETP) gene predicts future cardiovascular death in patients experiencing an acute coronary syndrome

Cholesterol ester transfer protein (CETP) plays a pivotal role in the remodelling of triglyceride (TG)-rich and high-density lipoprotein (HDL) particles. Sequence variations in the CETP gene may interfere with coronary atherosclerosis. However, clinical studies of various CETP polymorphisms have shown controversial data in coronary artery outcome. We aimed to investigate whether TaqIB CETP gene polymorphism could predict clinical outcome in a prospective cohort of patients hospitalized for an acute coronary syndrome (ACS). Two hundred and seventy consecutive Caucasian patients hospitalized for an ACS, and having a significant coronary artery disease in at least one major vessel (stenosis >50%), were prospectively enrolled and followed for 57 months. The mean age was 65.1+/-12.5 years, and 77% were males. One hundred and thirty-nine patients (51.5%) suffered from unstable angina at inclusion and 131 patients (48.5%) presented with an acute myocardial infarction (MI). The follow-up data were obtained from questionnaires. The major recurrent events recorded were 32 deaths comprising 28 cardiovascular deaths and 49 combined cardiovascular events (28 cardiovascular deaths, 19 non-fatal ACS and 2 non-fatal strokes). CETP genotyping was performed using a restriction fragment length polymorphism based method. A significant relation was found between B2B2 genotype and combined cardiovascular end-point (p<0.02), mainly driven by a link with cardiovascular death (p<0.05). The hazard risk ratio for cardiovascular death associated with B2B2 genotype was 2.2 [95% confidence interval (CI): 1.01-4.94, p<0.05]. In multivariate analyses, no modification except for a significant interaction with statin therapy was observed by inclusion of potential confounders for the association of B2B2 genotype with cardiovascular death. These results suggest that patients homozygous for the B2 allele and not taking statin had a strong increase of recurrent cardiovascular event after an initial acute coronary event. This cardiovascular risk seems to be corrected with statin therapy.

Association of the cholesteryl ester transfer protein Taq1 B2B2 genotype with higher high-density lipoprotein cholesterol concentrations and lower risk of coronary artery disease in a Tunisian population

The role of cholesteryl ester transfer protein (CETP) in the development of atherosclerosis is undergoing debate. In this prospective study, we sought to explore the role of the CETP Taq1B variant in coronary artery disease risk, and its association with plasma lipid and apolipoprotein concentrations. DNA was extracted from 316 patients undergoing coronary angiography. The Taq1B polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Lipid and apolipoprotein concentrations were measured by enzymatic and nephelometric assays. In our study population, the B2 allele frequency was 0.29. B2 allele carriers had a significantly higher high-density lipoprotein cholesterol (HDL-C) concentration than those with the B1B1 genotype (1.041+/-0.294 versus 0.995+/-0.277; p=0.039). After adjusting for age, sex, smoking status, diabetes, hypertension and dyslipidaemia, the odds ratio (OR) for significant stenosis associated with the B2 allele was 0.82 (95% confidence interval (CI) 0.60-0.97; p=0.039), suggesting that the B2 allele is associated with an 18% lower risk of significant stenosis. This protective effect seemed to be more significant in male nonsmokers (38% lower risk; OR 0.62, 95% CI 0.29-0.92; p=0.029). No significant protective effects were observed in women or male smokers. Our data suggest that the B2 allele is associated with higher concentrations of HDL-C, which confer a protective effect with regard to coronary atherosclerosis. This effect seems to be more significant in men than in women and in nonsmokers than in smokers.

Association of TaqIB Polymorphism in the Cholesteryl Ester Transfer Protein Gene With Serum Lipid Levels in the Guangxi Hei Yi Zhuang and Han Populations

BackgroundCholesteryl ester transfer protein (CETP) plays an important role in lipoprotein metabolism. The present study was undertaken to compare the difference in the CETP TaqIB gene polymorphism and its association...

P3-273: Cholesteryl ester transfer protein (CETP) Taq1B polymorphism is not associated with cognitive phenotype in a memory clinic sample

P3-273: Cholesteryl ester transfer protein (CETP) Taq1B polymorphism is not associated with cognitive phenotype in a memory clinic sample

Association of Cholesteryl Ester Transfer Protein Genotypes With CETP Mass and Activity, Lipid Levels, and Coronary Risk

The importance of the cholesteryl ester transfer protein (CETP) pathway in coronary disease is uncertain. Study of CETP genotypes can help better understand the relevance of this pathway to lipid metabolism and disease risk. To assess associations of CETP genotypes with CETP phenotypes, lipid levels, and coronary risk. Studies published between January 1970 and January 2008 were identified through computer-based and manual searches using MEDLINE, EMBASE, BIOSIS, Science Citation Index, and the Chinese National Knowledge Infrastructure Database. Previously unreported studies were sought through correspondence with investigators. Relevant studies related principally to 3 common (TaqIB [rs708272], I405V [rs5882], and -629C>A [rs1800775]) and 3 uncommon (D442G [rs2303790], -631C>A [rs1800776], and R451Q [rs1800777]) CETP polymorphisms. Information on CETP genotypes, CETP phenotypes, lipid levels, coronary disease, and study characteristics was abstracted from publications, supplied by investigators, or both. Ninety-two studies had data on CETP phenotypes, lipid levels, or both in 113,833 healthy participants, and 46 studies had data on 27,196 coronary cases and 55,338 controls. For each A allele inherited, individuals with the TaqIB polymorphism had lower mean CETP mass (-9.7%; 95% confidence interval [CI], -11.7% to -7.8%), lower mean CETP activity (-8.6%; 95% CI, -13.0% to -4.1%), higher mean high-density lipoprotein cholesterol (HDL-C) concentrations (4.5%; 95% CI, 3.8%-5.2%), and higher mean apolipoprotein A-I concentrations (2.4%; 95% CI, 1.6%-3.2%). The pattern of findings was very similar with the I405V and -629C>A polymorphisms. The combined per-allele odds ratios (ORs) for coronary disease were 0.95 (95% CI, 0.92-0.99) for TaqIB, 0.94 (95% CI, 0.89-1.00) for I405V, and 0.95 (95% CI, 0.91-1.00) for -629C>A. Three CETP genotypes that are associated with moderate inhibition of CETP activity (and, therefore, modestly higher HDL-C levels) show weakly inverse associations with coronary risk. The ORs for coronary disease were compatible with the expected reductions in risk for equivalent increases in HDL-C concentration in available prospective studies.

Common Variation in the CETP Gene and the Implications for Cardiovascular Disease and its Treatment: An Updated Analysis

Human plasma contains cholesteryl ester transfer protein (CETP) which, besides other functions, enables the transfer of cholesteryl esters in plasma from high-density lipoproteins (HDL) towards triglyceride-rich lipoproteins, thereby contributing to lower HDL cholesterol. Variations in the CETP gene, including the intronic TaqIB polymorphism (rs708272), are common in the population. Although HDL cholesterol is approximately 10% higher in TaqIB B2B2 than in B1B1 carriers, the association of this polymorphism with cardiovascular disease has not been unequivocally established. We present an updated pooled analysis concerning the association of cardiovascular disease with the TaqIB polymorphism, including only studies that predominantly comprise Caucasian subjects. The distribution of this CETP genotype was observed to be different in population-based studies (n = 10,526) compared with studies in populations selected by high cardiovascular risk (n = 10,947), with B2B2 carriers being less frequent among cases from high-risk populations compared with cases from population-based studies (p = 0.0009 for the difference in genotype distribution). In population-based studies, the odds ratio (OR) for cardiovascular disease was found to be 1.45 (95% CI: 1.07-1.95) in B2B2 compared with B1B1 carriers, contrasting the lower OR of 0.84 (95% CI: 0.74-0.96) in B2B2 versus B1B1 carriers from high-risk populations. Thus, it is possible that in the general population, the B2 allele is associated with higher cardiovascular risk, despite higher HDL cholesterol. Our analysis agrees with the contention that selection towards a lower frequency of B2B2 homozygotes may have occurred in selected populations, which would result in a apparently protective effect of the B2 allele when determined in high-risk populations. We also evaluated whether the TaqIB polymorphism would predict efficacy of lipid-lowering treatment with respect to plasma lipids and cardiovascular outcome, but the results of published studies were contradictory. Likewise, no definite conclusion can be made at present concerning the effect of this CETP polymorphism on the lipid response to diet intervention.

-141C Ins/Del polymorphism of the dopamine D2 receptor gene is associated with schizophrenia in a Spanish population

In this study we examined the relationship between dopamine D2 receptor (DRD2) polymorphisms (TaqIA, TaqIB, -141C Ins/Del) and dopamine D3 receptor (DRD3) Ser9Gly polymorphism and the risk of schizophrenia in a Spanish population. Two hundred and forty-three schizophrenia patients and 291 healthy controls from the general population participated in a case-control study. No significant differences were observed in the allele or genotype frequencies of TaqIA, TaqIB or Ser9Gly polymorphisms between the schizophrenia patients and the healthy controls. The frequency of the -141C Del allele was significantly lower in the former group (odds ratio=0.4, P=0.01). The -141C Del allele, which produces lower expression of DRD2, may protect against dopaminergic hyperactivity in schizophrenia. This study is one of the few studies of Caucasian participants that supports the results obtained in the original Japanese study, in which the -141C Ins/Del polymorphism was first described. Furthermore, our findings reinforce the hypothesis that excess dopaminergic activity leads to schizophrenia.

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.

Association between cholesteryl ester transfer protein Taq1B polymorphism with lipid levels in primary hyperlipidemic patients

AbstractPrimary hyperlipidemia, characterized by hypertriacylglycerolemia and/or hypercholesterolemia, is considered to be one of the most important risk factors for atherosclerosis and coronary heart disease. This study was performed by using polymerase chain reaction and restriction fragment length polymorphism analysis. We measured lipids and cholesteryl ester transfer protein (CETP) activity in primary hyperlipidemic and normolipidemic subjects, with and without Taq1B polymorphism. Genotype distribution and allelic frequencies of polymorphism were determined and compared in both groups. Our results showed that plasma CETP activity was significantly higher in primary hyperlipidemia than in controls (p = 0.001). Plasma lipids were also remarkably increased in primary hyperlipidemic subjects. In both patient and control groups, individuals with B1B1 and B1B2 genotypes had higher plasma CETP activity, lower total cholesterol, lower high‐density lipoprotein cholesterol and higher triacylglycerol than those with the B2B2 genotype. The values of low‐density lipoprotein cholesterol were significantly increased in primary hyperlipidemic patients with the B2B2 genotype. The genotype and allelic frequencies for this polymorphism differed significantly between primary hyperlipidemic patients and controls (p = 0.022 and p = 0.039, respectively). Taq1B polymorphism of the CETP gene was associated with changes in lipid profile and plasma CETP activity in the selected population.