Evaluation of digestive tolerance of a soluble corn fibre.

BACKGROUND: To assess consumers' acceptance of a new fibre, it is essential to evaluate its digestive tolerance after ingestion. We aimed to determine the tolerance of increasing dosages of Promitor™ Soluble Gluco Fibre (SGF; Tate&Lyle, Hoffman Estates, IL, USA) up to 70 g fibre per day using a validated gastrointestinal composite score. METHODS: A composite score of gastrointestinal tolerance integrating gastrointestinal symptoms, stool frequency and consistency was applied. To statistically validate this composite score, the gastrointestinal tolerance of inulin (10 g versus 20 g containing, respectively, 9 g versus 18 g of fibre) was assessed in 18 healthy volunteers in a randomised double-blind placebo-controlled cross-over study. Second, in a double-blind placebo-controlled cross-over study with 20 healthy volunteers, the gastrointestinal tolerance of SGF in both acute and 'spread over the day' conditions of consumption was assessed. RESULTS: By contrast to 10 g, 20 g of inulin demonstrated a significant difference in composite score compared to placebo [P < 0.001, difference = 7.6; 95% confidence interval (CI) = 3.8-11.3]. These values were considered as reference during the second study. In acute conditions, 40 g of SGF fibre was the highest (threshold) dose tested that indicates the digestive tolerance criteria (difference from placebo on the composite score <7.6 and upper limit of the 95% CI <11.3); this is twice the amount tolerated for inulin. In 'spread over the day' conditions, 65 g of SGF fibre was the threshold dose (P < 0.001, difference = 6.5; 95% CI = 3.4-9.5). CONCLUSIONS: The results of the present study demonstrate that 40 g of SGF fibre, when consumed as a single dose, and 65 g of SGF fibre, when consumed in multiple-doses, across the day are well-tolerated by healthy volunteers.

A fully validated simple new method for environmental monitoring by surface sampling for cytotoxics.

A wipe sampling procedure followed by a simple ultra-performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for simultaneous quantification of six cytotoxic drugs: 5-fluorouracil (5FU), doxorubicin (DOXO), epirubicin (EPI), ifosfamide (IF), cyclophosphamide (CP) and gemcitabine (GEM), as surrogate markers for occupational exposure. After a solid-phase extraction of wiping filter on 10 × 10 cm surface, the separation was performed within 6.5 min, using a gradient mobile phase and the analytes were detected by mass spectrometry in the multiple reaction ion monitoring mode. The method was validated according to the recommendations of the US Food and Drug Administration. The method was linear (r2 > 0.9912) between 2.5 and 200 ng per wiping sample (25 to 2000 pg/cm2) for 5FU, doxorubicin and epirubicin and between 0.2 and 40 ng per wiping sample (2 to 400 pg/cm2) for cyclophosphamide, ifosfamide and gemcitabine. The lower limits of quantification were 2.5 ng (25 pg/ cm2) for 5FU, doxorubicin and epirubicin, and 0.2 ng (2 pg/cm2) for CP, IF and GEM. Within-day and between-day imprecisions were <14.0, 10.6, 11.1, 8.7, 11.2 and 10.9% for 5-fluorouracil, doxorubicin, epirubicin, ifosfamide cyclophosphamide and gemcitabine, respectively. The inaccuracies did not exceed 2.7, 10.9, 1.1, 4.5, 1.6 and 2.9% for the studied molecules, respectively. This new sensitive validated method for surface contamination studies of cytotoxics was successfully applied on different localizations in hospital. This approach is particularly suitable to assess occupational exposure risk to cytotoxic drugs.

Diabetes and dyslipidaemia are associated with oxidative stress independently of inflammation in long-term antiretroviral-treated HIV-infected patients.

AIM: Ageing HIV-infected patients controlled by antiretroviral therapy (ART) frequently present age-related comorbidities, such as cardiovascular (CV) events, diabetes, dyslipidaemia, hypertension and chronic kidney disease (CKD). The prevalence of these comorbidities was evaluated in a cohort of long-term-monitored ART-controlled HIV-infected patients, then followed by a search into whether oxidative stress, like inflammation, might be associated with metabolic parameters and/or comorbidities. METHODS: Included were 352 long-term ART patients who started with protease inhibitors (PIs) in 1997-1999. They were evaluated at their final visit, 11 years later, for previous CV events, prevalence of diabetes, LDL-related and atherogenic (high TG/HDL) dyslipidaemias, hypertension and CKD. Also measured were circulating biomarkers to explore oxidative stress (Lp-PLA2, oxLDL, oxLDL/LDL ratio, paraoxonase and arylesterase activities), inflammation/immune activation (hsCRP, hsIL-6, D dimer, soluble CD14, ß2 microglobulin, cystatin C), adipokines and insulin resistance. Levels were compared in patients with and without each comorbidity or condition using non-parametric correlation tests and multivariate adjusted analyses. RESULTS: At the final visit, 81.5% of patients were male and were aged (median, IQR) 49 years (45-56); BMI was 23.0 kg/m2 (21.1-25.4), CD4+ lymphocytes were 620 cells/mm3 (453-790) and 91.5% had undetectable HIV-1 viral loads. The prevalence of diabetes was 11%, and LDL-related dyslipidaemia 28%, atherogenic dyslipidaemia 9%, hypertension 28%, CKD 9% and previous CV events 9%. Diabetes and atherogenic dyslipidaemia were associated with increased oxidative stress and independently with inflammation. LDL-related dyslipidaemia and impaired fasting glucose were associated with increased oxidative stress. No association of these biomarkers was detected with hypertension, CKD and previous CV events. CONCLUSION: In long-term-treated HIV-infected patients with frequent comorbid conditions, oxidative stress could be contributing to diabetes and LDL-related and atherogenic dyslipidaemias independently of inflammation.

[PPAR alpha-L162V, frequency and relationship with type 2 diabetes among black Senegalese people]. / PPARalpha-L162V: fréquence et relation avec le diabète de type 2 dans une population noire sénégalaise.

PPARs are supposed to be involved in pathogenesis of diabetes and its complications. According to some authors, L162V PPARalpha gene polymorphism would be associated to dyslipidemia susceptibility during diabetes, whereas for some authors, it rather would confer resistance to these metabolic abnormalities. The aim of this study is to search the relationship between this polymorphism and the occurrence of diabetes and its complications within a Senegalese black population constituted of 261 diabetic and 128 controls, by comparing alleles frequencies. Genomic analysis for alleles identification has been performed by the allelic discrimination technic TaqMan 5' Nuclease, after DNA extraction (Nucleon Bacc2. Amersham Int.). The results of genetic variants analysis revealed that L162V PPARalpha polymorphism would not be present among Senegalese black population, and consequently, should not be involved in diabetes onset.

Low-density lipoprotein for delivery of an acrylophenone antineoplastic molecule into malignant cells.

In vitro and in vivo data have indicated that tumor cells actively internalize the low-density lipoprotein (LDL) from the circulation. A family of 2-(aminomethyl) acrylophenones (AMA) possesses an in vitro antileukemic activity but is devoid of any in vivo antineoplastic activity, because the compounds are actively captured by proteins in solution in the blood. In order to achieve a selective delivery of these drugs via the LDL pathway, we have incorporated an AMA drug, 2-morpholinomethyl-2',3',4'- trimethoxy acrylophenone hydrochloride (ILE) into LDL particles. ILE spontaneously associated with LDL to produce an LDL-ILE complex containing 200 +/- 100 molecules of drug per LDL particle. The LDL-ILE complex was highly electronegative as detected by electrophoresis. Further, this complex presented an immunologically detected over expression of the ligand-binding domain to the LDL receptor. In spite of these modifications, the LDL receptor processing bound, internalized, and degraded the LDL-ILE complex. Nevertheless, these biological properties were reduced by 32, 20, and 40%, respectively, in comparison to native LDL. Despite its high electronegativity, the LDL-ILE complex was not recognized by the macrophagic scavenger receptor. The LDL-ILE complex showed specific LDL receptor mediated in vitro cytotoxicity as judged from the growth inhibition of neoplastic A549 cells and of normal fibroblasts, but no activity on defective LDL receptor cells. Further, the pharmacological activity of the complex against A549 cells has been demonstrated to be equally potent as that of the free drug (median inhibitory dose, 5 microM). It is suggested that LDL drug targeting of AMA molecules could specifically deliver active molecules to cancer cells, avoiding their entrapment by other blood proteins and their rapid clearance by the reticuloendothelial system.

Isolation and characterization of human Lp-B lipoprotein containing apolipoprotein B as the sole apolipoprotein.

A sequential immunoaffinity chromatography procedure was developed to isolate from whole normolipidemic human plasma a subpopulation of apoB containing particles (Lp-B) which is virtually free of non apoB protein. The absence of non apoB protein in Lp-B was assessed by enzyme immunoassay against apolipoproteins A-I, A-II, A-IV, E, C-III and (a). Electron microscopy and fractionation of the isolated particles by gel filtration demonstrated that these particles were heterogeneous in size. However, most of them had diameters between 18 and 26 nm. These particles were found to be rich in cholesterol (molar ratio cholesterol/apoB = 2246 +/- 995) poor in triacylglycerol (molar ratio triacylglycerol/apoB = 555 +/- 518) and had a phospholipids/apoB molar ratio of 713 +/- 348. Most of the cholesterol was esterified (66% +/- 5%). Lp-B particles bound to the apoB, E receptor of HeLa cells with a lower affinity than LDL prepared by ultracentrifugation (1.030 kg/l less than d less than 1.053 kg/l). (KD = 18.9 vs 10.5 nmol/l).

Isolation and characterization of two sub-species of Lp(a), one containing apo E and one free of apo E.

Lipoprotein Lp(a) was isolated by immunoaffinity chromatography using anti apolipoprotein B and anti apolipoprotein (a) immunosorbents. Besides apolipoproteins (a) and B, this fraction was shown to contain apolipoproteins C and E. Therefore, it was decided to further purify this crude Lp(a) into particles containing apolipoprotein E and particles free of apo E, using chromatography with an anti apolipoprotein E immunosorbent. Lp(a), free of apolipoprotein E was cholesterol ester rich and triacylglycerol poor and was found mainly in the LDL size range. In contrast, Lp(a) containing apolipoprotein E was triacylglycerol rich and was distributed mainly in the VLDL and IDL size range. Binding of these two fractions, one containing apo E and one free of it, to the apo B/E receptor of HeLa cells was studied. Both fractions bound to the receptor but the one containing apo E had a better affinity than the one free of apo E. Further studies are needed to identify the clinical importance of these two different entities.

Identification of apoB-containing lipoprotein families in NIDDM.

The purpose of this study was to determine the concentrations and composition of apoB-containing lipoprotein families in whole plasma and major lipoprotein density classes of a selected group of Native Americans from northeastern Oklahoma with non-insulin-dependent diabetes mellitus. The measurement of lipoprotein density classes showed that the total lipoprotein mass of very-low-density lipoproteins was significantly higher and that of high-density lipoproteins significantly lower in diabetic patients than nondiabetic control subjects regardless of their plasma triglyceride levels. The VLDLs were enriched with TG, free cholesterol, and apolipoproteins C-III and E. HDLs were enriched with TG but depleted of apoC-III and apoE. There was no change in the levels of TG-enriched low-density lipoproteins. Fractionation of VLDL by sequential immunoprecipitation with antisera to apoE and apoC-III established that increased concentrations of this density class in diabetic patients are due to elevated levels of TG-rich lipoprotein LP-B:C and lipoprotein LP-B:C:E. The levels of LP-B:C particles were increased more than the levels of LP-B:C:E particles. The LDLs were characterized by a slight increase in TG-enriched lipoprotein B and no change in the levels of LP-B:C and LP-B:C:E. There was no difference between diabetic patients with or without vascular disease in the levels of LP-B and LP-B:C:E. However, patients with vascular disease had higher concentrations of LP-B:C particles in VLDL and whole plasma than patients without vascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Accumulation of triglyceride-rich lipoprotein in subjects with abdominal obesity: the biguanides and the prevention of the risk of obesity (BIGPRO) 1 study.

The present study represents a new insight into the Biguanides and the Prevention of the Risk of Obesity (BIGPRO) 1 study population at inclusion. This population, selected basically on the basis of a high waist-to-hip ratio (>/=0.95 for men and >/=0.80 for women), is supposed to represent a group of patients with insulin resistance. The present study was undergone to establish whether apolipoprotein C-III (apoC-III) and apolipoprotein E (apoE) associated with apo B (apoC-III LpB and apoE LpB, respectively), considered to be markers of remnant accumulation, play a role in the hypertriglyceridemia associated with insulin resistance and whether they are related to other biological abnormalities frequently observed in this syndrome. In this population, the concentration of the markers of remnant accumulation increases with triglyceride levels. Therefore, correlation studies were realized to assess the relative effect of insulin and the markers of remnant accumulation on triglyceride plasma level. As a first attempt, a simple correlation analysis revealed that insulin is positively related to the markers of remnant accumulation only in hypertriglyceridemic patients (triglycerides >/=1.7 mmol/L). To assess the independent contribution of these markers, insulin, and other parameters related to the plasma triglyceride concentration, a stepwise multiple regression analysis was run. Results revealed that insulin and the markers of remnant accumulation (specifically, apoE LpB) are independent contributors to the plasma triglyceride concentration. Markers of the endothelial damage, plasminogen activator inhibitor-1, tissue plasminogen activator, and von Willebrand factor, which are often increased in the case of insulin resistance, were tested for their correlation with the markers of remnant accumulation. Plasminogen activator inhibitor-1 is positively correlated with these markers only in hypertriglyceridemic male subjects. It is concluded that increased insulin levels found in insulin resistance syndrome are associated with an increased production of triglyceride-rich lipoproteins enriched in apoC-III and apoE. The accumulation of these remnants and/or their abnormal composition in apoC-III and apoE could be an explanation for the development of hypertriglyceridemia in this syndrome.

The effect of metformin on the metabolic abnormalities associated with upper-body fat distribution. BIGPRO Study Group.

OBJECTIVE: The constellation of anomalies associated with insulin resistance is a plausible additional cause of ischemic cardiovascular disease and of NIDDM. To test this hypothesis in a primary prevention trial, the effects of metformin as a potential candidate for intervention in the insulin resistance syndrome (IRS) were evaluated in 324 middle-aged subjects with upper-body obesity. RESEARCH DESIGN AND METHODS: Trial patients were selected on the basis of a high waist-to-hip ratio. They were randomly allocated to receive either metformin or placebo, following a double-blind procedure. After 1 year of treatment, the main clinical and biological parameters of the IRS were assessed and their evolution compared between treatment groups. RESULTS: Compared with placebo, metformin induced a significant weight loss, a better maintenance of fasting blood glucose, total and LDL cholesterol levels, and a greater decrease of fasting plasma insulin concentration. Moreover, tissue-type plasminogen activator antigen, a marker of fibrinolytic impairment, showed a significant decrease under metformin. By contrast, metformin treatment had no significant effect on blood pressure or serum triglyceride and HDL cholesterol concentrations. The main side effect of metformin was diarrhea. CONCLUSIONS: The BIGuanides and Prevention of Risks in Obesity (BIGPRO1) results suggest that metformin would be a suitable candidate for long-term intervention for the prevention of diabetes but that its use in a trial of primary prevention of cardiovascular diseases requires either a reevaluation of its properties toward the most potentially atherogenic anomalies of the IRS or a better definition of the target population.

Effect of phytosterols/stanols on LDL concentration and other surrogate markers of cardiovascular risk.

Plant sterols and stanols are well-known to reduce LDL-cholesterol (LDL-C) concentrations. It is generally accepted that supplementation with 2g/day of sterols/stanols leads to a 10% reduction in LDL. However, most of the clinical trials supporting this conclusion were of short-term duration, and the results of longer interventions are scanty. In four studies, interventions lasting>6 months were carried out and the LDL-C-lowering effects were maintained over this longer duration, although some results suggest that a reduced effect may be observed with sterols, while stanols maintain their effect. In any case, the data are too limited to be definitive. In a free-living population as well as in multiparametric interventional studies, however, the LDL-C-lowering effect has been confirmed, although to a lesser extent than in clinical studies. In the absence of data on cardiovascular morbidity and mortality, data for surrogate markers of cardiovascular risk could be considered adequate alternatives. Several studies have been conducted on this basis, but their results failed to demonstrate any favourable effects. The present report summarizes the different results obtained in long-term studies, and in those comparing the effects of sterols and stanols on lipids and other surrogate markers of cardiovascular risk.

In vivo evidence for the role of lipoprotein lipase activity in the regulation of apolipoprotein AI metabolism: a kinetic study in control subjects and patients with type II diabetes mellitus.

The aim of this study was to delineate the role of lipoprotein lipase (LPL) activity in the kinetic alterations of high density lipoprotein (HDL) metabolism in patients with type II diabetes mellitus compared with controls. The kinetics of HDL were studied by endogenous labeling of HDL apolipoprotein AI (HDL-apo AI) using a primed infusion of D(3)-leucine. The HDL-apo AI fractional catabolic rate (FCR) was significantly increased (0.32 +/- 0.07 vs. 0.23 +/- 0.05 pool/day; P < 0.01), and HDL composition was changed [HDL cholesterol, 0.77 +/- 0.16 vs. 1.19 +/- 0.37 mmol/L (P < 0.05); HDL triglycerides, 0.19 +/- 0.12 vs. 0.10 +/- 0.03 mmol/L (P < 0.05)] in diabetic patients compared with healthy subjects. HDL-apo AI FCR was correlated to plasma and HDL triglyceride concentrations (r = 0.82; P < 0.05 and r = 0.80; P < 0.05, respectively) and to homeostasis model assessment (r = 0.78; P < 0.05). Postheparin plasma LPL activity was decreased in type II diabetes (6.8 +/- 2.8 vs. 18.1 +/- 5.2 micromol/mL postheparin plasma.h; P < 0.005) compared with that in healthy subjects and was correlated to the FCR of HDL-apo AI (r = -0.63; P < 0.05). LPL activity was also correlated with HDL cholesterol (r = 0.78; P < 0.05), plasma and HDL triglycerides (r = -0.87; P < 0.005 and r = -0.83; P < 0.05, respectively), and homeostasis model assessment (r = -0.79; P < 0.05). In addition, the LPL to hepatic lipase ratio was correlated with the catabolic rate of HDL (r = -0.76; P < 0.06). These results suggest that a decrease in the LPL to hepatic lipase ratio in type II diabetes mellitus, mainly related to lowered LPL activity, could induce an increase in HDL catabolism. These alterations in HDL kinetics in type II diabetes proceed to some extent from changes in their composition, probably linked to an increase in triglyceride transfer from very low density lipoprotein particles, in close relationship with LPL activity and resistance to insulin.

Lipoprotein metabolism in marasmic children of northern Mauritania.

Lipid metabolism in marasmus has been poorly studied compared with that in kwashiorkor. Published studies show normal or high plasma triglycerides and low cholesterol concentrations. We studied some plasma lipid indexes, including total, HDL, and LDL cholesterol; triglycerides; apolipoproteins A-I, A-II, B, C-III, and E; and lipoprotein particles containing apo A-I, apo A-I and A-II (Lp A-I:A-II) Lp C-III:B, and Lp E:B in Mauritanian marasmic children compared with a control group. We found in patients low total, HDL, and LDL cholesterol and normal Lp A-I concentrations, which suggest that the cholesterol reverse transport system is not altered. We observed normal triglyceride concentrations and significantly increased Lp C-III:B and Lp E:B, which are triglyceride-rich particles. These data suggest that the marasmic state led to quantitative and structural modifications of the triglyceride-rich lipoproteins, defined by their apolipoprotein composition, and was probably related to undercatabolism.

Lowering of HDL2-cholesterol and lipoprotein A-I particle levels by increasing the ratio of polyunsaturated to saturated fatty acids.

The protective role of high-density lipoproteins (HDLs) has been attributed to the subfractions HDL2 (according to the density) and lipoprotein A-I (LpA-I) (according to the composition in apolipoproteins). We investigated the effect of a high ratio of polyunsaturated to saturated fatty acids (P:S) on these subfractions in a homogeneous group of young adult males. Two prescribed diets were consumed successively at the subjects' homes for 3 wk each in a random order; one diet contained 70 g butter (P:S 0.2, diet B), the other contained 70 g sunflower margarine (P:S 1.1, diet M). Total calorie, fat, and cholesterol intakes were similar for the two diets. Cholesterol and apolipoprotein B in serum and in low-density lipoproteins (LDLs) were lower with diet M than with diet B. However, significant decreases in protective subfractions of HDL, HDL2, and LpA-I were observed. This undesirable effect of the diet with a high P:S could cancel the benefits of lowering the LDL-cholesterol concentrations.

n-3 polyunsaturated fatty acids raise low-density lipoproteins, high-density lipoprotein 2, and plasminogen-activator inhibitor in healthy young men.

The effects of a moderate supplementation in n-3 polyunsaturated fatty acids (PUFAs) were investigated in 36 young healthy adult males. Factors investigated were lipoprotein (including HDL subfractions and apolipoproteins) and hemostasis indexes, assessed by platelet aggregation and plasminogen-activator-inhibitor (PAI) activity. Fat-controlled diets were prescribed, one with and one without a fish-oil supplement (control diet), successively during 3 wk in random order. Total calorie, fat, and cholesterol intakes were similar in the two diets. Triglycerides in serum and very-low-density lipoproteins were lower and high-density-lipoprotein 2 cholesterol was higher with the n-3 PUFA-supplemented diet. These effects as well as a significant decrease in platelet aggregation can be considered beneficial in terms of cardiovascular risk. However, significant increases in low-density-lipoprotein cholesterol and PAI activity occurred and were correlated. This latter effect could be detrimental.

The relationship between apolipoprotein AI-containing lipoprotein fractions and environmental factors: the prospective epidemiological study of myocardial infarction (PRIME study).

Apolipoprotein (apo) AI is distributed within high-density lipoproteins (HDL) between different types of particles, one containing both apoAI and apoAII (LpAI:AII), the other containing no apoAII (LpAI). We investigated the associations between LpAI and LpAI:AII with several factors such as body mass index (BMI), waist to hip ratio (WHR), alcohol intake, cigarette consumption and physical activity, in three French and one Northern Irish male populations included in a prospective study (PRIME study). LpAI and LpAI:AII were associated with variations in all environmental factors, except LpAI:AII, which was not associated with WHR. These relationships were unchanged after adjustment for other environmental factors, but slightly modified after adjustment for triglyceride levels. LpAI decreased when BMI, WHR and cigarette smoking increased, and increased with alcohol consumption and physical activity. LpAI:AII had a similar variation except for the absence of LpAI:AII modification associated with WHR variation. The associations between LpAI and BMI, alcohol consumption and cigarette smoking were largely dependent on HDL-cholesterol as indicated by the lack of any significance when the adjustment for HDL-cholesterol was made. Conversely, after adjustment for HDL-cholesterol, the significant association between LpAI:AII and BMI disappeared, while the associations between LpAI:AII and alcohol consumption, cigarette smoking and physical activity remained significant. These results suggest that the mechanisms of LpAI and LpAI:AII modulations differ according to each environmental factor, some dependent on the lipid content of lipoproteins and others not, but LpAI and LpAI:AII levels seem independent of triglyceride concentration.

Distribution of lipid variables in subjects in Belfast, Northern Ireland and Taiyuan, P R China.

To compare the plasma lipid, lipoprotein and apolipoprotein profiles of people of Chinese and European origin, a sample of 151 male Chinese subjects was selected from Taiyuan, Shanxi Province, P R China to 202 broadly age-matched subjects in Belfast who were selected as controls in a case-control study of myocardial infarction. Mean total cholesterol (TC) was 6.15 mmol/l in Belfast and 4.28 mmol/l in Taiyuan. Low density lipoprotein cholesterol (LDL) was much higher in Belfast. High density lipoprotein cholesterol (LDL) was also higher in Belfast than in Taiyuan but the ratio of HDL to TC was lower in Belfast than Taiyuan. Triglyceride (TG) levels were similar and this was reflected in the relatively high level of apolipoprotein E (apo E) in the Chinese sample.

Plasma apolipoprotein A-I, A-II, B, E and C-III containing particles in men with premature coronary artery disease.

Lipoprotein (Lp) cholesterol and apolipoproteins (apo) A-I and B levels have been shown to be better markers for the presence of coronary artery disease than total cholesterol. In this study, we determined the plasma levels of lipoprotein particles containing apo A-I only (LpA-I), apo A-I and A-II (LpA-I:A-II), apo B and C-III (LpB:C-III) and apo B and E (LpB:E) in 145 patients with coronary artery disease (mean age +/- SD, 51 +/- 7 years) and 135 healthy control men (mean age 49 +/- 11 years). Patients with CAD had lower high density lipoprotein (HDL) cholesterol and apo A-I levels and higher triglycerides and apo had lower high density lipoprotein (HDL) cholesterol and apo A-I levels and higher triglycerides and apo B levels than controls. In patients with CAD, LpA-I (0.341 +/- 0.093 vs. 0.461 +/- 148 g/l) and LpA-I:A-II (0.694 +/- 0.171 vs. 0.899 +/- 0.148 g/l) were lower, whereas LpB:E (0.372 +/- 0.204 vs. 0.235 +/- 0.184 g/l) were higher than in controls (cases vs. controls, all P less than 0.005). No significant differences were observed for LpB:C-III (0.098 +/- 0.057 vs. 0.107 +/- 0.061 g/l, p = 0.235) particles. Discriminant analysis indicates that LpA-II:A-I, LpE:B, LpA-I, and triglycerides best differentiate between cases and controls. Plasma apo C-III (0.027 +/- 0.008 vs. 0.036 +/- 0.020 g/l) and E (0.040 +/- 0.015 vs. 0.055 +/- 0.029 g/l) were lower in the CAD group (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of apolipoprotein E between apo B- and non apo B-containing lipoproteins according to apo E phenotype.

Apolipoprotein E (apo E) is a component of all the classes of lipoproteins and can be distributed among apo B- (LpB) and non apo B-containing lipoproteins (Lp-non-B). Using a new electroimmunoassay kit, plasma apo E, apo E in Lp-non-B (apo E-Lp-non-B) and apo E in LpB (apo E-LpB) levels were measured in healthy control subjects (n=481) from 3 centers participating in the ECTIM study (Etude Cas-Témoins sur l'Infarctus du Myocarde), a population-based study on myocardial infarction. The distribution of apo E among lipoproteins was analyzed according to the apo E phenotype after adjustment for center, body mass index, tobacco use, alcohol consumption and triglycerides. Apo E was higher (average excess: + 0.32; P < 0.0001) and lower (average excess: -0.12; P < 0.0001) in subjects carrying the allele epsilon2 and the allele epsilon4 respectively, than in apo E3/3 subjects. These differences are the consequence of variations in apo E-Lp-non-B which clearly differed between the groups classified according to their apo E phenotype (P < 0.0001). The average excess of apo E Lp non-B compared to apo E3/3 subjects was + 0.43 (P < 0.0001) and -0.22 (P < 0.0001) for the epsilon2 and epsilon4 alleles respectively. Apo E-LpB was lower in subjects carrying the epsilon2 allele (P < 0.02) while the presence of the epsilon4 allele did not modify this parameter. The proportion of apo E within HDL was clearly higher and lower in subjects carrying apo E2 and apo E4 respectively than in apo E3/3 subjects. Although triglyceride levels were dependent on the apo E phenotype, the adjustment of the proportion of apo E in HDL for triglycerides hardly modified the results. For the first time, these results, using direct measurements on a large number of subjects, confirm the greater preference of apo E4 over apo E2 for LpB and vice versa for Lp-non-B. They also show a greater affinity of apo E2 for HDL compared to apo E3. This high affinity of apo E2 for HDL could be due to the formation of the apo E-A-II complex. These results indicate that apo E phenotype modulates the distribution of apo E among lipoproteins and suggest differences in lipoprotein metabolism between apo E2, apo E3 and apo E4.

The Gln/Arg polymorphism of human paraoxonase (PON 192) is not related to myocardial infarction in the ECTIM Study.

Paraoxonase is a high-density-lipoprotein associated enzyme capable of hydrolyzing lipid peroxides, which has been suggested to contribute to atherosclerosis and coronary heart disease (CHD). We studied the Gln/Arg polymorphism affecting codon 192 of human paraoxonase (PON 192) to determine whether this polymorphism, which is associated with serum paraoxonase (PON) activity, represents a risk factor for myocardial infarction (MI). The PON 192 polymorphism was analysed in 642 male patients with myocardial infarction and 701 age-matched controls participating in the ECTIM Study (Etude Cas-Témoins de l'Infarctus du Myocarde). The frequency of the Gln allele was 0.69 in cases and 0.70 in controls (ns). The frequency of the PON 192/Arg allele in 405 MI patients who underwent coronary angiography was 0.295, 0.323 and 0.331, respectively in those with 1, 2 or 3 stenosed arteries (stenosis > 50%) (ns). The mean levels of several plasma lipids, lipoproteins and apolipoproteins were compared between the 3 PON genotypes and no difference was observed. The PON 192 polymorphism was unrelated to MI, the severity of coronary atherosclerosis and to plasma levels of several lipid variables.