BACKGROUND

Acipimox, a derivative of nicotinic acid, lowers serum lipid levels by reducing the production of very-low-density and low-density lipoproteins (LDL).

METHODS

We studied the additional lipid-lowering effect of high doses of acipimox in 12 patients with severe familial hypercholesterolemia (FH) who were on treatment with an HMG CoA reductase inhibitor, in some cases in combination with a resin.

RESULTS

There was a significant reduction in total serum cholesterol (-9%), LDL-cholesterol (-9%) and serum triglycerides (-21%) when the standard doses of acipimox (750 mg/day) was added to treatment with simvastatin (and a resin). However, higher doses had no further hypolipidemic effect. In concordance with the reduction of serum cholesterol and LDL-cholesterol there was a significant decrease in apolipoprotein (apo)-B (-11%). There was no change in HDL-cholesterol, apo-A1 and lipoprotein(a). Acipimox in high doses up to 2250 mg/d was well tolerated except for initial gastric complaints and of flushing; because of these side effects one patient dropped out of the study.

CONCLUSIONS

Acipimox in high doses, which were well tolerated, has no additional lowering effect on LDL-levels compared to the standard dose in patients with severe FH who are already treated with simvastatin.

In 216 healthy subjects (74 endurance trained persons, 87 variably trained subjects and 55 sedentary individuals) the behaviour of triglycerides, total cholesterol, lipoproteins and apolipoproteins in blood serum - all in relation to physical performance capacity - were determined in the early morning under fasting conditions. HDL-/total cholesterol (%) as well as the ratios LDL/HDL and Apo A1/Apo A2 proved to have the highest selectivity. Only marginal differences or none at all between the groups were found for Apo B, Apo A2 and total cholesterol. In an analysis of correlation the strongest relation with physical performance was found for HDL-/total cholesterol (%), Apo A1/Apo A2, Apo A1 and LDL/HDL. No significant correlations were found for total-cholesterol, Apo B and Apo A2. When the influence of age and body weight was excluded in an analysis of partial correlation Apo A1 showed the strongest relation to physical performance. The relevant partial correlations for Apo A1/Apo A2, HDL-cholesterol and HDL-/total cholesterol (%) were found to be weaker. With regard to the influence of increased physical activity on the human lipid metabolism it was concluded that the determination of lipoproteins can be significantly supplemented by the determination of apolipoproteins. The behaviour of Apo A1 and Apo A1/Apo A2 indicates that enhanced physical activity increases the vasoprotective HDL2 subfraction.

In previous short-term studies in rats and humans, the ingestion of raw wheat germ lowered plasma triglycerides and cholesterol. Thus, the present study was designed to investigate the possible long-term effects of wheat germ intake. Diet supplementation with raw wheat germ or partially defatted wheat germ was tested in two separate groups of 10 and 9 free-living human subjects, respectively. They all exhibited hypercholesterolemia (6.14-9.67 mmol/L cholesterol) and 11 had hypertriglyceridemia. None was diabetic. Fasting blood samples were taken at the beginning of the study, after 4 wk of 20 g/d wheat germ intake, after 14 additional weeks of 30 g/d wheat germ intake and after 12 wk without any supplementation. Dietary records were kept for seven and three consecutive days, before and during the wheat germ intake periods, respectively. Raw wheat germ intake significantly decreased plasma cholesterol (-8.7%) and tended to reduce VLDL cholesterol (-19.6%) after 4 wk. After 14 additional weeks, plasma cholesterol (-7.2%) and LDL cholesterol (-15.4%) remained lower and plasma triglycerides (-11.3%) tended to be lower. The apo B:apo A1 ratio significantly decreased after both periods. Partially defatted wheat germ transiently decreased plasma triglycerides and cholesterol after a 4-wk intake. The present data indicate that wheat germ reduces cholesterolemia in the long term and could play a beneficial role in the dietary management of type IIa and IIb hyperlipidemia.

Recent epidemiological studies have shown some beneficial health effects of the long chain (n-3) polyunsaturated fatty acids found in fatty fish. Although the results of these studies are often ambiguous and inconclusive, they have prompted many intervention trials to study the effects of n-3 fatty acids (FA) on the cardiovascular risk profile. However screening of the literature revealed that many of the beneficial effects of fish (oil) were obtained in intervention studies which had several serious shortcomings in their design. Therefore we started a placebo controlled randomised trial with increasing doses of n-3FA (respectively 0; 1.12; 2.24 and 3.37 g n-3 FA/day) and in order to have a maximum compliance this study was done in healthy monks. Fifty eight subjects took the fish oil capsules during 12 months and were thereafter followed for another 6 months. We couldn't detect any effect of n-3 FA supplementation on total cholesterol, HDL cholesterol, LDL cholesterol, apo A1, Lp(a), HbA1C, glucose, fibrinogen, factor VIII, antithrombin III, plasminogen activator inhibitor, tissue plasminogen activator and von Willebrand factor concentration, on bleeding time or on systolic or diastolic blood pressure. A pronounced significant dose dependent decrease of triglyceride levels was seen, while a slight but statistical significant decrease of apo B levels was observed in the highest fish oil dose. As the importance of triglycerides in the pathogenesis of atherosclerosis is still under discussion, the clinical relevance of these finding is not clear at the moment. It seems therefore improbable that the anti-atherosclerotic action of n-3 FA is due to an effect on the lipid, apoprotein, coagulation or fibrinolysis parameters as measured in our study. Hence further research must be focused on other parameters (prostaglandins) which can be influenced by n-3 FA and which probably play an equally important role in the atherosclerotic process.

Two series of 100 subjects each, males and females, have been studied for the determination of plasma values of apo-A1, the major peptide of HDL, and of apo-B, the major peptide of LDL. To minimize a possible influence of variations in plasma lipid levels, two series of subjects were selected with very similar mean values of plasma cholesterol and triglyceride. Despite this criterion of selection apo-A1 was significantly lower in males (127 +/- 18 mg/l) than in females (137 +/- 15 mg/l) while the reverse was true for apo-B (99 +/- 16 mg/l in males vs. 91 +/- mg/l in females). Both apo-B and apo-A1 showed a tendency to increase with advancing age with the greatest increase for apo-A1 (in both sexes) and for apo-B (only in males) from the 3rd to the 4th decade of age.

The effects of 6 weeks of heavy and moderate ethanol feeding to rats upon lipids and lipoprotein metabolism were determined. As compared to the control group, the heavy ethanol feeding resulted in the following changes: liver weight/kilogram body weight increased by 48% (p less than 0.001) with a concomitant 52% increase (p less than 0.001) in liver protein/kilogram body weight and a 2.75-fold (p less than 0.001) increase in liver total lipids/kilogram body weight. In contrast, liver DNA/kilogram body weight or per liver was not affected significantly. Plasma cholesterol and triglycerides were higher by 53% (p less than 0.01) and 77% (p less than 0.01), respectively. Liver cholesterol and triglycerides were 4.4-fold and 3.8-fold higher (p less than 0.001), respectively. Plasma total A1 was 1.72-fold higher (p less than 0.001), whereas there was no significant difference in plasma apo E levels between the two groups. However, plasma high density lipoproteins (HDl) apo E was 48% lower (p less than 0.02) while the very low density lipoproteins (VLDL) E was 2.15-fold higher (p less than 0.02). Hepatic total protein synthetic rate in the ethanol group was not significantly different from the control group. In contrast, labeled leucine incorporation into the total secretory proteins was inhibited by 36% (p less than 0.01) in ethanol-fed group.(ABSTRACT TRUNCATED AT 250 WORDS)

BACKGROUND

Associations between variations in the lymphotoxin-alpha (LTA) gene and coronary artery disease (CAD) and type 2 diabetes have previously been reported. We investigated the influence of the LTA 252A>G and 804C>A polymorphisms on circulating parameters related to metabolic syndrome in Korean patients with CAD.

METHODS

The study subjects comprised 446 Korean male patients with CAD (age 53.9 y, BMI 25.2 kg/m2).

RESULTS

The LTA 252A>G and 804C>A polymorphisms were almost in complete linkage disequilibrium (R(2)=99.4%). The LTA 252A>G polymorphism was associated with LDL particle size (P=0.046), HOMA-IR (P=0.022) and circulating levels of triglyceride (P=0.006), HDL-cholesterol (P=0.008), apo A1 (P=0.031), insulin (P=0.046), and adiponectin (P=0.018), after adjustment for BMI. CAD patients with LTA 252G/G (n=96) had a lower concentration of HDL-cholesterol, a smaller LDL particle size, and a higher triglyceride level, compared to those with 252A/A (n=121) or 252A/G (n=229). In addition, CAD patients with LTA 252G/G had lower concentrations of adiponectin and higher levels of insulin, and HOMA-IR than those with 252A/A.

CONCLUSIONS

Homozygosity for rare alleles of the LTA 252A>G polymorphisms was associated with features of metabolic syndrome such as hyperinsulinemia, dyslipidemia, small LDL particle and low adiponectin level in CAD patients, suggesting that CAD patients with LTA 252GG are at high risk and needed an intensive intervention against further progression.

OBJECTIVE

To determine whether modestly severe obesity modifies glucose homeostasis, levels of cardiometabolic markers, and HDL function in African Americans (AAs) and white Americans (WAs) with prediabetes.

METHODS

We studied 145 subjects with prediabetes (N = 61 WAs, N = 84 AAs, mean age 46.5 ± 11.2 years, mean BMI 37.8 ± 6.3 kg/m(2)). We measured fasting levels of lipids, lipoproteins, and an inflammatory marker (C-reactive protein [CRP]); HDL functionality (i.e., levels of paraoxonase 1 [PON1]); and levels of oxidized LDL, adiponectin, and interleukin-6 (IL-6). We measured serum levels of glucose, insulin, and C-peptide during an oral glucose tolerance test. Values for insulin sensitivity index (Si), glucose effectiveness index (Sg), glucose effectiveness at zero insulin (GEZI), and acute insulin response to glucose (AIRg) were derived using a frequently sampled intravenous glucose tolerance test (using MINMOD software).

RESULTS

Mean levels of fasting and incremental serum glucose, insulin, and C-peptide tended to be higher in WAs versus AAs. The mean Si was not different in WAs versus AAs (2.6 ± 2.3 vs. 2.9 ± 3.0 × 10(-4) × min(-1) [μU/mL](-1)). Mean values for AIRg and disposition index as well as Sg and GEZI were lower in WAs than AAs. WAs had higher serum triglyceride levels than AAs (116.1 ± 55.5 vs. 82.7 ± 44.2 mg/dL, P = 0.0002). Mean levels of apolipoprotein (apo) A1, HDL cholesterol, PON1, oxidized LDL, CRP, adiponectin, and IL-6 were not significantly different in obese AAs versus WAs with prediabetes.

CONCLUSIONS

Modestly severe obesity attenuated the ethnic differences in Si, but not in Sg and triglyceride levels in WAs and AAs with prediabetes. Despite the lower Si and PON1 values, AAs preserved paradoxical relationships between the Si and HDL/apoA1/triglyceride ratios. We conclude that modestly severe obesity has differential effects on the pathogenic mechanisms underlying glucose homeostasis and atherogenesis in obese AAs and WAs with prediabetes.

OBJECTIVE

The association between Helicobacter pylori (H. pylori) infection and serum lipid profile is still controversial. The aim of this study was to determine any possible relationship between H. pylori infection and the lipid profile of patients with upper gastrointestinal symptoms.

METHODS

Consecutively selected 20-70 year-old dyspeptic patients who had undergone esophagogastroduodenoscopy were evaluated for H. pylori infection using both the CLO test and Giemsa staining. Serum total cholesterol (C), HDL-C, LDL-C, apo-A1, apo-B and triglyceride levels were measured.

RESULTS

A total of 137 patients (median age 52.0 years) were studied. Total cholesterol levels were lower in H. pylori-infected patients than in H. pylori-negative patients (mean +/- SEM: 199.3 +/- 5.9 versus 212.6 +/- 4.6 mg/dl, p = 0.08). Patients with duodenal ulcer (DU) had significantly lower levels of all measured lipidemic parameters including cholesterol, with the exception of triglycerides, in comparison with either H. pylori-positive or -negative dyspeptic patients (cholesterol: 177.6 +/- 6.5 versus 214.6 +/- 4.2 mg/dl, p < 0.0001). However, there was no difference in the total cholesterol/HDL-C ratio between DU patients and the rest of the dyspeptic patients.

CONCLUSIONS

Among H. pylori-positive and H. pylori-negative patients there was no difference in lipid profile apart from a trend towards total cholesterol levels being lower in H. pylori-positive patients. However, cholesterol, HDL-C, LDL-C, apo-A and apo-B were all decreased in DU patients even though this reduction did not result in a fall in the total cholesterol/HDL-C ratio. The etiologic factor differentiating the lipid profiles among dyspeptics only in H. pylori-positive patients carrying a DU could be dietetic, microbial, genetic or a combination of all three.

OBJECTIVE

This study is amid at investigating the associations, and interactions of serum lipid biomarkers with microvascular complications of type 2 diabetes (T2D).

METHODS

A nested case-control study was conducted within an ongoing prospective study on patients with T2D. Microvascular complications of T2D including diabetic neuropathy, diabetic retinopathy and diabetic nephropathy were investigated. A total of 444 cases with at least one of the microvascular complications of T2D and 439 age- and gender-matched controls free of any of the chronic microvascular complications of T2D were included. The associations and interactions of a panel of serum lipid biomarkers with the microvascular complications of T2D were investigated.

RESULTS

Serum triglyceride had the strongest association with microvascular complications of T2D (crude model: β=0.632, P value=0.045). Each standard deviation increment in serum TG was associated with 3.7 times increased frequency of microvascular complications. Despite high density lipoprotein cholesterol (HDL-C), serum apolipoprotein A1 (Apo A1) was positively associated with the presence of diabetic neuropathy. Each standard deviation increment in serum ApoA1 was associated with increased frequency of diabetic neuropathy (OR, 1.2, 95% CI, (1.1-1.3), P value=0.006). The frequency of diabetic neuropathy was higher in 2nd and 3rd quartiles of serum Lp(a) compared to diabetic patients in the first quartile (OR, 5.52, 95% (1.17-25.8), P value=0.047).

CONCLUSIONS

ApoA1 but not HDL-C is straightly associated with diabetic neuropathy. Even Slight rise in serum Lp(a) is associated with increased frequency of diabetic retinopathLipid variables could serve as specific predictors of vascular complications in diabetes.

The effect of sphingomyelin hydrolysis on triacylglycerol-rich lipoprotein secretion was examined in the human intestinal cell line, CaCo-2. Addition of sphingomyelinase decreased sphingomyelin and phosphatidylethanolamine by 60 and 20%, respectively. Sphingomyelin hydrolysis decreased the basolateral secretion of triacylglycerol mass, newly synthesized triacylglycerol, and apo B mass. Pulse-chase experiments with [35S]methionine demonstrated a decrease in apo B synthesis and a marked decrease in apo B100 and apo B48 secretion without altering apo A1 secretion. Sphingomyelin hydrolysis did not change apo B mRNA levels nor apo B turnover. Phosphatidylcholine-specific phospholipase C did not decrease apo B synthesis or its basolateral secretion. Membrane protein kinase C (PKC) activity was decreased twofold after sphingomyelin hydrolysis. The PKC inhibitor staurosporine decreased apo B mass and newly synthesized apo B secretion. Sphingomyelinase and staurosporine together caused an additional decrease in apo B secretion suggesting that sphingomyelin hydrolysis decreased apo B secretion independently of its effect on PKC activity. Moreover, conditions that increase PKC activity did not increase apo B secretion. Cell-permeable analogs of ceramide decreased immunoreactive apo B secretion. Sphingosine was without effect. The hydrolysis of membrane sphingomyelin by intestinal or pancreatic neutral sphingomyelinase may lead to the accumulation of cellular ceramide, which, in turn, could inhibit triacylglycerol-rich lipoprotein secretion.

The aim of this multicentre study was to investigate the effect--in everyday life--of long term administration of acarbose on parameters of glycaemic control, daily insulin requirements, lipid parameters and tolerability in ambulant type 1 diabetic subjects insufficiently controlled with diet and insulin. Furthermore, effects on lipid parameters were to be studied. A total of 16 patients withdrew from the study, 13 of these during the acarbose medication period. For four of these 13 patients the adverse event started during the placebo run-in period. The data of 62 patients (35 men and 27 women, mean age 38 (range 18-64) years, median duration of diabetes 10 (range 1-40) years) were valid for statistical analysis. The median daily dose of acarbose at the final assessment (i.e. after 16 weeks of active treatment) was 200 (range 75-300) mg. During the placebo run-in period HbA1c levels tended to decrease from 8.9 +/- 1.1 to 8.5 +/- 0.9%. After 8 and 16 weeks of acarbose treatment the mean level had decreased further to 8.1 +/- 0.9 and 8.2 +/- 0.9%, respectively (both P < 0.001). After stopping acarbose HbA1c levels increased again to a mean level of 8.6 +/- 0.9%. Mean levels of HbA1c per centre followed the same profile. Seven-point blood glucose profiles followed the same pattern. None of these changes over time reached statistical significance except for a significant drop during acarbose treatment of the time-point 90 min after lunch (P < 0.01). After stopping acarbose treatment values returned to pre-study levels. For total cholesterol, HDL-cholesterol, triglycerides, Apo A1 and Apo B, and Lp(a) no significant changes were observed. Daily insulin dose was 48 (range 26-92) U at the start of the study and did not change. The most frequent reported adverse events were flatulence (43%), diarrhoea (27%), and abdominal pain (11%). We conclude that acarbose up to 3 x 100 mg/day can be a valuable adjunct to insulin in improving metabolic control in persons with type 1 diabetes.

Recent development of proteomic array technology, including protein profiling coupling ProteinChip array with surface-enhanced laser desorption ionization time-of-flight mass spectrometry (SELDI-TOF/MS), provides a potentially powerful tool for discovery of new biomarkers by comparison of its profiles according to patient phenotypes. We used this approach to identify the host factors associated with treatment response in patients with chronic hepatitis C (CHC) receiving a 48-wk course of pegylated interferon (PEG-IFN) alpha 2b plus ribavirin (RBV). Protein profiles of pretreatment serum samples from 32 patients with genotype 1b and high viral load were conducted by SELDI-TOF/MS by using the three different ProteinChip arrays (CM10, Q10, IMAC30). Proteins showed significantly different peak intensities between sustained virological responders (SVRs), and non-SVRs were identified by chromatography, SDS-PAGE, TOF/MS and tandem mass spectrometry (MS/MS) assay. Eleven peak intensities were significantly different between SVRs and non-SVRs. The three SVR-increased peaks could be identified as two apolipoprotein (Apo) fragments and albumin and, among the eight non-SVR-increased proteins, four peaks identified as two iron-related and two fibrogenesis-related protein fragments, respectively. Multivariate analysis showed that the serum ferritin and three peak intensity values (Apo A1, hemopexin and transferrin) were independent variables associated with SVRs, and the area under the receiver operating characteristic (ROC) curves for SVR prediction by using the Apo A1/hemopexin and hemopexin/transferrin were 0.964 and 0.936. In conclusion, pretreatment serum protein profiling by SELDI-TOF/MS is variable for identification of response-related host factors, which are useful for treatment efficacy prediction in CHC receiving PEG-IFN plus RBV. Our data also may help us understand the mechanism for treatment resistance and development of more effective antiviral therapy targeted toward the modulation of lipogenesis or iron homeostasis in CHC patients.

The authors present 5 cases of paradoxical depression of high-density lipoprotein (HDL) cholesterol induced by fibrate drugs. In a 24-month review of all cases seen in one physician's practice at the Winnipeg Health Sciences Centre Lipid Clinic, 492 patients made a total of 1187 visits. Sixty-eight of them were given a fibrate drug (14%). Ten patients had HDL cholesterol levels that were less than 0.5 mmol/L (2%), and of these, 5 cases were due to exposure to fenofibrate (1%). These 5 cases comprised 7.4% of the 68 patients who were given any fibrate drug during that period. Mean levels were as follows: HDL cholesterol on fenofibrate 0.27, off fenofibrate 1.0 mmol/L and apo A1 on fenofibrate 0.41, off fenofibrate 1.17 g/L. A literature review revealed documented cases in 37 patients involving fibrates alone or in combination with other drugs known to cause decreased HDL cholesterol levels. In 13 patients, exposure was to fibrate therapy alone; in those exposed to combinations, the effect was clearly attributable to fibrates in 9; in 14, the nonfibrates (mostly rosiglitazone) were the attributable drugs; and in 1, it was impossible to tell. Thus, fibrate therapy should always be suspected as a cause of profoundly depressed HDL cholesterol.

Oral isotretinoin has been reported to increase serum total triglycerides (TG), cholesterol (TC), phospholipids (TPL), apoprotein B (apo B), and to reduce high-density lipoprotein cholesterol (HDL-C). To investigate the effects of isotretinoin on HDL, we measured HDL-C, HDL phospholipids (HDL-PL), apoprotein A1 (apo A-1), and HDL-C subfractions (HDL2-C and HDL3-C) in 24 healthy, male patients receiving a 16-week course of isotretinoin (1.0 mg/kg/day) for treatment of severe acne vulgaris. Patients were placed on a constant diet and fasting lipid parameters were measured every 4 weeks. Analysis of the data from the 20 patients who completed the study confirmed the reported increase in TG, TC, LDL-C, apo B, and LDL-C/HDL-C (all p less than 0.01) observed during isotretinoin therapy. Reduction occurred in HDL-C (p less than 0.05) and HDL2-C (p less than 0.01) while HDL3-C remained unchanged, indicating that the effect of isotretinoin is on the HDL2-C subfraction. Apo A-1 and HDL-PL did not change significantly, suggesting that the reduction in HDL-C represents cholesterol depletion of the HDL particle rather than a reduction in HDL mass. After discontinuing isotretinoin, serum lipid parameters returned to baseline levels.

Eccentric exercise has been shown to exert beneficial effects in both lipid profile and insulin sensitivity. Antioxidant supplementation during chronic exercise is controversial as it may prevent the physiological training-induced adaptations. The aim of this study was to investigate: 1) the minimum duration of the eccentric exercise training required before changes on metabolic parameters are observed and 2) whether antioxidant supplementation during training would interfere with these adaptations. Sixteen young healthy men were randomized into the Vit group (1 g of vitamin C and 400 IU vitamin E daily) and the placebo (PL) group. Subjects received the supplementation for 9 weeks. During weeks 5-9 all participants went through an eccentric exercise training protocol consisting of two exercise sessions (5 sets of 15 eccentric maximal voluntary contractions) per week. Plasma triglycerides (TG), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), apolipoproteins (Apo A1, Apo B and Lpa) and insulin sensitivity (HOMA) were assessed before the supplementation (week 0), at weeks 5, 6, 7, 8 and 9. TG, TC and LDL were significantly lower compared to pre supplementation at both weeks 8 and 9 (P<0.05) in both groups. HDL was significantly elevated after 4 weeks of training (p < 0.005) in both groups. There was no effect of the antioxidant supplementation in any of the variables. There was no effect of either the training or the supplementation protocol in apolipoproteins levels and insulin sensitivity. A minimum duration of 3 weeks of eccentric exercise training is required before beneficial effects in lipid profile can be observed in healthy young men. Concomitant antioxidant supplementation does not interfere with the training-induced adaptations.

The hypolipidemic agents, phthalimide, saccharin, o-(N-phthalimido) acetophenone, N-(p-chlorobenzoyl) sulfamate, and o-chlorobenzylsulfonamide affected low-density lipoprotein (LDL) and high-density lipoprotein (HDL) receptor activity and lipoprotein degradation. In isolated rat hepatocytes, rat aorta foam cells, and human fibroblasts, LDL receptor activity, which is dependent on apo-B and -E, was inhibited by the drugs in a dose-dependent manner. LDL degradation was accelerated in the hepatocytes, while it was inhibited in aorta cells and fibroblasts. The drugs enhanced HDL receptor activity, dependent on apo-E and -A1, and HDL degradation in the hepatocytes, whereas in fibroblasts and aorta cells HDL receptor binding and degradation were suppressed. In parallel, activities of acyl CoA acyl transferase, sn-glycerol-3-phosphate acyl transferase, and heparin-induced lipoprotein lipase decreased and activities of HMG-CoA reductase and cholesterol oleate-ester hydrolase increased. In fibroblasts the presence of drugs enhanced HDL binding of intracellular cholesterol. In vivo studies demonstrated that phthalimide and saccharin treatment enhanced the clearance of HDL and decreased the clearance of LDL from the serum of rats. The results suggest that the mode of action of the agents is to modulate the lipoprotein receptor and, thereby, the clearance of lipids from peripheral tissue as part of the hypolipidemic activity.

BACKGROUND

The association of ATP binding cassette transporter G8 gene (ABCG8) rs4148217 single nucleotide polymorphism (SNP) and serum lipid profiles is still controversial in diverse racial/ethnic groups. Mulao nationality is an isolated minority in China. The aim of this study was to evaluate the association of ABCG8 rs4148217 SNP and several environmental factors with serum lipid levels in the Guangxi Mulao and Han populations.

METHODS

A total of 634 subjects of Mulao nationality and 717 participants of Han nationality were randomly selected from our previous samples. Genotyping of the ABCG8 rs4148217 SNP was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing.

RESULTS

The genotypic and allelic frequencies of ABCG8 rs4148217 SNP were different between the two nationalities (P < 0.01 for each), the frequency of A allele was higher in Mulao than in Han. The A allele carriers in Han had lower high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (Apo) A1 levels than the A allele noncarriers (P < 0.05 for each), whereas the A allele carriers in Mulao had lower ApoA1 levels than the A allele noncarriers (P < 0.05). Subgroup analyses showed that the A allele carriers in Han had lower HDL-C and higher triglyceride (TG) levels in females but not in males than the A allele noncarriers (P < 0.05 for each), and the A allele carriers in Mulao had lower ApoA1 levels in females but not in males than the A allele noncarriers (P < 0.05). The levels of TG and HDL-C in Han, and ApoA1 in Mulao were associated with genotypes in females but not in males (P < 0.05-0.01). Serum lipid parameters were also correlated with several environmental factors (P < 0.05-0.001).

CONCLUSIONS

The ABCG8 rs4148217 SNP is associated with serum TG, HDL-C and ApoA1 levels in our study populations, but this association is different between the Mulao and Han populations. There is a sex (female)-specific association in both ethnic groups.

Early alterations in glucose homeostasis increase the risk of developing insulin resistance and obesity later in life. The concurrence of altered lipids and insulin sensitivity/resistance markers at birth has been scarcely investigated. The study aimed to ascertain level ranges of homocysteine (tHcyt), arylesterase (AE), lipids/lipoproteins, and insulin resistance/sensitivity markers in full-term neonates and to determine the concurrence effect of dyslipaemia and dysglycaemia on those parameters at birth. Participants were 197 full-term, 2.5 to <4.0 kg, without foetal distress Spanish newborns from the Mérida Study. Parameter percentiles for males and females were stated. The effect of the concurrence high glucose/high triglycerides (high glucose/high TG) or high glucose/low cholesterol transported by HDL (HDL-c) on tHcyt, LDL-c, HDL-c, lipoprotein (a) (Lp(a)), oxidised LDL (oxLDL), AE, glucose, insulin sensitivity (QUICKI) and insulin resistance index (HOMA-IR) was studied. Females had higher total cholesterol (TC), HDL-c, Apo A1, Lp(a) and HDL-c/Apo A1, but lower relative transport of TC (%TC) by the very low lipoprotein fraction than males. No gender differences were found for glucose, HOMA-IR and QUICKI. Neonates at the 2.5- to 2.999-kg range display more adequate HOMA-IR and QUICKI levels that their >3.0 kg counterparts. The concurrence of high glucose/high TG or high glucose/low HDL-c increased TC/HDL-c and HOMA-IR, but decreased, oxLDL, oxLDL/LDL-c and QUICKI with respect to that of low glucose/low TG or glucose/high HDL-c. The concurrence glucose/TG has predictive value for low QUICKI, whilst that of glucose/HDL-c for low QUICKI and high HOMA-IR, suggesting the importance of routine TG, HDL-c and glucose screening at birth as it would identify candidates for insulin resistance.

A recent prospective study has suggested that increased plasma viscosity may be associated with higher risk of coronary heart disease. A longitudinal approach was used to investigate associations between plasma viscosity and conventional risk factors in an apparently healthy French population aged 45-56 years (637 men and 431 women) over a 2-year follow-up period. In univariate analysis, change in plasma viscosity was significantly related to changes in smoking status, systolic and diastolic blood pressure, gamma glutamyl transferase (gamma GT), body mass index and triglycerides only in men, and to changes in total cholesterol, low-density lipoprotein (LDL) cholesterol and apolipoprotein (apo) B in both sexes. Change in plasma viscosity was also significantly associated with changes in fibrinogen and hemoglobin levels in both sexes. No association was found with age, high-density lipoprotein (HDL) cholesterol or apo A1 in both sexes, or with changes in smoking and menopausal status in women. In multiple stepwise regression analysis, independent determinants of change in plasma viscosity were changes in smoking status, systolic blood pressure, gamma GT, total cholesterol, fibrinogen and hemoglobin in men, and changes in fibrinogen and apo B in women. These results strengthen the hypothesis that increased plasma viscosity may be one of the mechanisms linking conventional risk factors to the risk of cardiovascular disease and suggest that its decrease may be obtained by appropriate life-style changes.

Epidemiologic studies have reported that exposure to arsenic (As) is associated with higher risk of cardiovascular disease (i.e., coronary heart disease and peripheral arterial heart disease) and mortality. This cross-sectional study aimed to compare serum lipid, lipoprotein, and apolipoprotein profiles in workers exposed to As. The subjects of this study included 57 workers exposed to As and 57 controls. Demographic characteristics and occupational information were collected through questionnaires. Exposure to As was assessed in indoor air of a workplace and determined using the creatinine values in the urine. Blood samples were collected using immunochemistry and nephelometry to measure the levels of total cholesterol (CHOL), triglycerides (TRIG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), lipoprotein(a) (Lp(a)), apolipoprotein-A1 (Apo-A1), and apolipoprotein-B (Apo-B). No significant difference in the demographic data was detected between the two groups. Urinary As concentration was significantly (p<0.001) higher in exposed subjects than in the controls (13.4±6.1 and 4.4±6.1μg/gCreat, respectively). No statistically significant differences were observed in CHOL, TRIG, HDL, and LDL concentrations between the two groups. Lp(a), Apo-B, and Apo-B/Apo-A1 ratio values were significantly higher and the Apo-A1 level was significantly lower in the exposed group than in the control subjects. Regression analysis highlighted a significant (p<0.001) association between urinary As and Lp(a), Apo-A1, and Apo-B concentration, and Apo-B/Apo-A1 ratio. This study revealed the influence of As on apolipoproteins, suggesting a potential risk of cardiovascular diseases in subjects exposed to low levels of As.

A new photosystem I core has been isolated that is devoid of the bound iron-sulfur clusters but preserves electron flow from P700 to the intermediate electron acceptor A1. The particle is prepared by incubation of a Synechococcus sp. PCC 6301 photosystem I core protein (which contains electron acceptors A0, A1, and FX) with 3 M urea and 5 mM K3Fe(CN)6 to oxidatively denature the FX iron-sulfur cluster to the level of zero-valence sulfur. In this apo-FX preparation, over 90% of the flash-induced absorption change at 820 nm decays with a 10-microseconds half-time characteristic of the decay of the P700 triplet state formed from the backreaction of P700+ with an acceptor earlier than FX. Chemical reduction at high pH values with aminoiminomethanesulfinic acid results in kinetics identical with those seen in the P700 chlorophyll a protein prepared with sodium dodecyl sulfate (SDS-CP1, which contains only electron acceptor A0); the flash-induced absorption change decays primarily with a 25-ns half-time characteristic of the backreaction between P700+ and A0-, and the magnitude of the total absorption change is larger than can be accounted for by the P700 content alone. Addition of oxygen results in a reversion to the 10-microseconds kinetic decay component attributed to the decay of the P700 triplet state. At 77 K, the optical transient in the apo-FX preparation decays with a 200-microseconds half-time characteristic of the backreaction between P700+ and A1-.(ABSTRACT TRUNCATED AT 250 WORDS)

The existence of marked elevations of ascitic fluid cholesterol has been observed in patients with peritoneal carcinomatosis compared to patients with cirrhosis and has been found useful in differential diagnosis. This finding could be caused by an enhanced movement of plasma lipoproteins into the peritoneal cavity. To test this hypothesis we determined the fasting concentrations of total, high density lipoprotein (HDL)- and low density lipoprotein (LDL)-cholesterol, apolipoprotein-A1 (apo-A1) and apolipoprotein-B (apo-B) in serum and ascites of 17 patients with cirrhosis and 16 patients with peritoneal carcinomatosis. The movement of proteins from plasma to ascites was calculated from the ascites/serum concentration ratios of six different sized proteins with a molecular mass ranging from 54 kDa to 971 kDa. Mean values (mg/dl) for total cholesterol (92.6 vs. 21.0), HDL-cholesterol (15.6 vs. 1.8), LDL-cholesterol (63.4 vs. 16.1), apo-A1 (50.2 vs. 13.6) and apo-B (41.2 vs. 12.9) in ascites were significantly higher in peritoneal carcinomatosis than in cirrhosis. These differences could only partially be explained by the higher serum concentrations of these parameters in peritoneal carcinomatosis, but were mainly due to a lower selectivity for the movement of plasma proteins and lipoproteins into ascites (mean ascites/serum (A/S) ratio: 0.30-0.77) in peritoneal carcinomatosis as compared to cirrhosis (mean ascites/serum ratio: 0.11-0.21). In both groups about 85% of the total cholesterol in serum and ascites consisted of HDL- and LDL-cholesterol. These findings support the hypothesis that elevations in ascitic cholesterol in peritoneal carcinomatosis compared to cirrhosis are mainly caused by the increased movement of plasma HDL and LDL into the peritoneal cavity.

Corn oil (CO) and extra-virgin olive oil (EVOO) are rich sources of unsaturated fatty acids (UFA), but UFA profiles differ among oils, which may affect lipoprotein levels.

The objective of this study was to assess the effects of CO versus EVOO intake on fasting lipoprotein and subfraction cholesterol levels, apolipoprotein (apo) A1, apo B, and low-density lipoprotein particle concentrations in men and women.

As part of a weight maintenance diet, men and women were provided with food items prepared with 54 g per day of CO or EVOO (21-day treatment, 21-day washout) in a randomized, double-blind, controlled-feeding, crossover trial. Fasting lipoprotein cholesterol and related variables were determined with density gradient ultracentrifugation.

Among the 54 completers, CO reduced total cholesterol, low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apo B and LDL particle concentration to a greater extent compared with EVOO intake. Changes in LDL-C and VLDL-C contributed to the larger reduction in non-HDL-C with CO compared with EVOO intake (-0.39 mmol/l vs -0.04 mmol/l; P<0.001). The larger reduction in LDL-C by CO intake was attributable to changes (P<0.05) caused by CO vs EVOO in large LDL1+2-C (-0.22 mmol/l) and intermediate-density lipoprotein cholesterol (-0.12 mmol/l). HDL-C responses did not differ between treatments, but apo A1 increased more with EVOO compared with CO intake (4.6 versus 0.7 mg/dl, respectively, P=0.016).

CO intake reduced atherogenic lipoprotein cholesterol and particle concentrations to a larger extent than did EVOO, which may have implications for cardiovascular disease risk.