Serum Lipoprotein Metabolism Research Articles

Association of rs662799 and rs5070 genetic polymorphisms with hypertriglyceridemia and atherogenic dyslipidemia in pediatric patients in Southeast Mexico

Background and aimsTriglycerides are the initiators of the metabolic changes that lead to atherogenic dyslipidemia (AD). The APOA5 and APOA1 genes are involved in the response and metabolism of serum lipids and lipoproteins, where single nucleotide polymorphisms (SNP) rs662799 (promoter region) and rs5070 (intronic region) have been associated with the susceptibility to dyslipidemia. Until now, few studies evaluate the association of these polymorphisms with the presentation of hypertriglyceridemia and AD among Mexican children. Therefore, the objective was to determine the association between rs662799 and rs5070 with hypertriglyceridemia and AD in a pediatric population of southeastern Mexico. Materials and methodsA case–control analysis was performed including 268 infants aged 2–16 years, anthropometric, clinical variables, and serum lipid profiles were analyzed. DNA was extracted from blood samples and genotyping of polymorphisms was executed with the TaqMan SNP genotyping assay. Allele and genotypic frequencies were calculated. For genetic association analysis, logistic regression models were fitted according to models of inheritance. ResultsThe SNP rs662799 (C) was significantly associated with hypertriglyceridemia in the overdominant model (OR=3.89, p=0.001) and AD in the dominant model (OR=4.01, p=0.001). The SNP rs5070 (T) has a protective effect against hypertriglyceridemia in the additive risk model (OR=0.68, p=0.03). ConclusionPolymorphism rs662799 was significantly associated with cases of hypertriglyceridemia and AD in minors in southeastern Mexico. On the other hand, rs5070 polymorphism was not associated with cases of hypertriglyceridemia or AD.

Hyperbaric Oxygen Therapy Ameliorates Sperm Parameters in Apolipoprotein E Knockout Mice Testes by Attenuating Oxidative Stress and Inflammation.

Apolipoprotein E (ApoE) is a member of apolipoprotein (apo) family and plays critical role in lipid metabolism. In this study, the relationship between abnormal lipid metabolism caused by ApoE-deficient and male reproduction was investigated. The effect of hyperbaric oxygen (HBO) therapy on 7-month-old ApoE-knockout male mice was assessed subsequently. Mice were randomly divided into 3 groups: control group (WT), ApoE (- / -) group (AP-CON), and ApoE (- / -) plus HBO group (AP-HBO), which received HBO treatment. We found that ApoE knockout caused a decrease in male reproductive capacity due to the reduced total sperm motility, progressive motility (PR), and lower blastocyst formation rate. HBO treatment could accelerate serum lipoprotein metabolism including LDL, T-CHO, and TG and semen quality. As a result, fertilization and blastocyst formation of AP-HBO group were higher than that of AP-CON, proving positive therapeutic effect. Mechanism exploration found that HBO treatment ameliorated the testicular microenvironment by attenuating inflammatory factor production and oxidative stress, eventually improved the sperm motility. Collectively, our study provided more evidences of HBO treatment for improving the semen quality of patients with abnormal lipid metabolism caused by ApoE-deficient.

Association of rs662799 and rs5070 genetic polymorphisms with hypertriglyceridemia and atherogenic dyslipidemia in pediatric patients in Southeast Mexico

Background and aimsTriglycerides are the initiators of the metabolic changes that lead to atherogenic dyslipidemia (AD). The APOA5 and APOA1 genes are involved in the response and metabolism of serum lipids and lipoproteins, where single nucleotide polymorphisms (SNP) rs662799 (promoter region) and rs5070 (intronic region) have been associated with the susceptibility to dyslipidemia. Until now, few studies evaluate the association of these polymorphisms with the presentation of hypertriglyceridemia and AD among Mexican children. Therefore, the objective was to determine the association between rs662799 and rs5070 with hypertriglyceridemia and AD in a pediatric population of southeastern Mexico. Materials and methodsA case–control analysis was performed including 268 infants aged 2–16 years, anthropometric, clinical variables, and serum lipid profiles were analyzed. DNA was extracted from blood samples and genotyping of polymorphisms was executed with the TaqMan SNP genotyping assay. Allele and genotypic frequencies were calculated. For genetic association analysis, logistic regression models were fitted according to models of inheritance. ResultsThe SNP rs662799 (C) was significantly associated with hypertriglyceridemia in the overdominant model (OR=3.89, p=0.001) and AD in the dominant model (OR=4.01, p=0.001). The SNP rs5070 (T) has a protective effect against hypertriglyceridemia in the additive risk model (OR=0.68, p=0.03). ConclusionPolymorphism rs662799 was significantly associated with cases of hypertriglyceridemia and AD in minors in southeastern Mexico. On the other hand, rs5070 polymorphism was not associated with cases of hypertriglyceridemia or AD.

Effect of Peptide Drug Liraglutide Nano-Formulation Combined with Sodium-Glucose Cotransporter-2 Inhibitor on Blood Lipids in Patients with Type 2 Diabetes.

With the aging of our population and the increase in the number of obese people, diabetes has become a common disease. At present, drug treatment is mainly used for diabetes. Dyslipidemia is the main cause of diabetes. The regulation of blood lipids in diabetic patients through drugs is the key to treating diabetes. The purpose of this article is to further explore the specific effect and mechanism of peptide drug liraglutide nano-formulation combined with sodium-glucose co-transporter-2(SGCT-2) inhibitor on blood lipids in patients with type 2 diabetes. This article uses 30 people included in our hospital in 2019 2 patients with type 2 diabetes are divided into the group of peptide drug liraglutide nano preparations, the group of SGCT-2 inhibitors and the peptide drug liraglutide nano preparations combined with SGCT-2. In the inhibitor combination medication group, patients were given drug intervention according to the group name with the consent of the patients. After three days, the serum cholesterol, triglyceride, lipoprotein and lipid metabolism levels of all patients were tested. The results showed that under the intervention of peptide drug liraglutide nanoparticles combined with SGCT-2 inhibitor, the cholesterol level of patients with type 2 diabetes decreased from (368.2 ± 8.3) mmol / L to (1978.4 ± 4.7) mmol/L, triglyceride level decreased from (653.7 ± 12.5) mg/dL to (426.8 ± 9.6) mg/dl, and lipid metabolism level increased by 25.6%. Therefore, it can be seen that the peptide drug liraglutide nano preparation combined with SGCT-2 inhibitor has a certain therapeutic effect on type 2 diabetes.

The Application Value of Lipoprotein Particle Numbers in the Diagnosis of HBV-Related Hepatocellular Carcinoma with BCLC Stage 0-A.

Early diagnosis is essential for improving the prognosis and survival of patients with hepatocellular carcinoma (HCC). This study aims to explore the clinical value of lipoprotein subfractions in the diagnosis of hepatitis B virus (HBV)-related HCC. Lipoprotein subfractions were detected by 1H-NMR spectroscopy, and the pattern-recognition method and binary logistic regression were performed to classify distinct serum profiles and construct prediction models for HCC diagnosis. Differentially expressed proteins associated with lipid metabolism were detected by LC-MS/MS, and the potential prognostic significance of the mRNA expression was evaluated by Kaplan–Meier survival analysis. The diagnostic panel constructed from the serum particle number of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL-1~LDL-6) achieved higher accuracy for the diagnosis of HBV-related HCC and HBV-related benign liver disease (LD) than that constructed from serum alpha-fetoprotein (AFP) alone in the training set (AUC: 0.850 vs. AUC: 0.831) and validation set (AUC: 0.926 vs. AUC: 0.833). Furthermore, the panel achieved good diagnostic performance in distinguishing AFP-negative HCC from AFP-negative LD (AUC: 0.773). We also found that lipoprotein lipase (LPL) transcript levels showed a significant increase in cancerous tissue and that high expression was significantly positively correlated with the poor prognosis of patients. Our research provides new insight for the development of diagnostic biomarkers for HCC, and abnormal lipid metabolism and LPL-mediated abnormal serum lipoprotein metabolism may be important factors in promoting HCC development.

135-OR: The Effect of Fixed-Dose Combination of Insulin Degludec and Liraglutide on Serum Lipoprotein Metabolism in Patients with Type 2 Diabetes Mellitus

Aim: Administration of fixed-dose combination of Insulin Degludec and Liraglutide (IDegLira) has been associated with changes in the lipid-profile of diabetic patients. We assessed the effect of IDegLira on serum apolipoproteins, apoB-containing lipoprotein subclasses and HDL lipidome in patients with type 2 diabetes mellitus (T2DM). Methods: Sixty uncontrolled patients with T2DM on oral antidiabetic drugs were included. Of them, thirty received IDegLira and the remaining Insulin Degludec(IDeg). Lipid and carbohydrate metabolism parameters were assessed before and following 3-month-treatment. ApoB-containing lipoprotein subclasses levels were measured by LDL-Lipoprint method, whereas HDL lipidomic analysis via 1H-NMR spectroscopy. Results: Administration of IDegLira resulted in a significant reduction of total (TC) and LDL cholesterol (LDLC) by 14.68mg/dl and 10.45mg/dl, respectively. ApoA1 and apoB decreased in patients treated with IDegLira. A non-significant change in small-dense LDLC (sdLDL-C) levels was observed that was significantly correlated with changes in TG levels (r=0.468, p=0.007). Furthermore, IDegLira administration resulted in significant enrichment of HDL particles’ core in esterified cholesterol and depletion of TGs content. IDegLira induced an atheroprotective shift in fatty acid pattern of HDLs characterized by a statistically significant lower content in saturated and higher in unsaturated fatty acids (linoleic acid, eicosapentaenoic and arachidonic acids and docosahexaenoic acid). No significant changes were observed in the IDeg group. Conclusions: Administration of IDegLira is accompanied by changes in HDL lipdome, a decrease in TC, LDLC, apoA1 and B, while the levels of sdLDL were only reduced in patients experiencing a decrease in TGs. The contribution of these changes to cardiovascular risk reduction after treatment with liraglutide in clinical trials cannot be excluded. Disclosure E. Pappa: None. C. Kostara: None. C. Tellis: None. A.D. Tselepis: None. E. Bairaktari: None. V. Tsimihodimos: None.

Consumption of high-dose vitamin C (1250 mg per day) enhances functional and structural properties of serum lipoprotein to improve anti-oxidant, anti-atherosclerotic, and anti-aging effects via regulation of anti-inflammatory microRNA.

Background Although the health effects of vitamin C are well known, its physiological effect on serum lipoproteins and microRNA still remain to be investigated, especially daily consumption of a high dosage. Objectives To investigate the physiological effect of vitamin C on serum lipoprotein metabolism in terms of its anti-oxidant and anti-glycation activities, and gene expression via microRNA regulation. Methods We analyzed blood parameters and lipoprotein parameters in young subjects (n = 46, 22 ± 2 years old) including smokers who consumed a high dose of vitamin C (1250 mg) daily for 8 weeks. Results Antioxidant activity of serum was enhanced with the elevation of Vit C content in plasma during 8 weeks consumption. In the LDL fraction, the apo-B48 band disappeared at 8 weeks post-consumption in all subjects. In the HDL fraction, apoA-I expression was enhanced by 20% at 8 weeks, especially in male smokers. In the lipoprotein fraction, all subjects showed significantly reduced contents of advanced glycated end products and reactive oxygen species (ROS). Triglyceride (TG) contents in each LDL and HDL fraction were significantly reduced in all groups following the Vit C consumption, suggesting that the lipoprotein was changed to be more anti-inflammatory and atherogenic properties. Phagocytosis of LDL, which was purified from each individual, into macrophages was significantly reduced at 8-weeks post-consumption of vitamin C. Anti-inflammatory and anti-senescence effects of HDL from all subjects were enhanced after the 8-weeks consumption. The expression level of microRNA 155 in HDL3 was reduced by 49% and 75% in non-smokers and smokers, respectively. Conclusion The daily consumption of a high dose of vitamin C for 8 weeks resulted in enhanced anti-senescence and anti-atherosclerotic effects via an improvement of lipoprotein parameters and microRNA expression through anti-oxidation and anti-glycation, especially in smokers.

Clinical Study on the Effect of Simvastatin on Butyrylcholinesterase Activity

Although the physiological function of serum butyrylcholinesterase (BuChE) has not yet been clarified, there is evidence that this enzyme is involved in serum lipoprotein metabolism. It has been suggested that serum BuChE is positively correlated with LDL (low-density lipoprotein) and negatively with HDL (high-density lipoprotein) levels. The objective of this study was to determine whether the activity of BuChE changes during treatment with simvastatin (CAS 79902-63-9). The effects of simvastatin therapy on serum lipoproteins and plasma BuChE activity were studied in 15 patients with type IIa and 17 patients with type IIb hyperlipoproteinemia. Beside the expected influence on serum lipid concentration, a statistically significant decrease in BuChE activity in patients with hyperlipoproteinemia type IIa and IIb during treatment with simvastatin was not observed.

Effect of increasing doses of Rosuvastatin and Atorvastatin on apolipoproteins, enzymes and lipid transfer proteins involved in lipoprotein metabolism and inflammatory parameters

This paper contains detailed results of a sub-population of the prospective randomized RADAR (Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport) study.Objective:Statin treatment results in substantially decreased incidence of cardiovascular events but the exact pathophysiological mechanism of their beneficial effect is yet unclear. We aimed to examine the effects of up-titrated doses of two widely used statins (atorvastatin (ATOR) and rosuvastatin (ROSU)) on parameters involved in lipoprotein metabolism, in patients with low high density lipoprotein cholesterol values (HDL-C).Research design and methods:In this RADAR substudy, 80 patients, aged 40–80 years, with known cardiovascular disease and low HDL-C (<1.0 mmol/l), were randomized to receive, after an initial 6 week dietary run-in phase, either ATOR 20 mg (n = 41) or ROSU 10 mg (n = 39). The doses were up-titrated (in 6 week intervals) to 80 mg of ATOR or 40 mg of ROSU at 12 weeks. Serum lipoproteins and lipoprotein metabolism parameters were measured at baseline and at 6 and 18 weeks of follow up.Results:Both statins significantly reduced total cholesterol (TChol) and non-HDL-C values with ROSU being more effective for the doses studied (p < 0.05). No statistically significant effect on HDL-C was observed for either statin. Apolipoproteins (apo) B, CI, CIII, AV and E were significantly reduced in both groups (p < 0.05), while the ratio of HDL particles containing both apoAI and apoAII (LpAI-AII) over HDL containing apoAI alone (LpAI) was changed for both statins with the decrease of LpAI being more prominent in the ATOR group (p = 0.028). Cholesterol ester transfer protein (CETP) mass and activity, phospholipid transfer protein (PLTP) activity and lipoprotein-associated phospholipase A2 (Lp-PLA2) mass and activity were all significantly reduced in both treatment groups over the follow-up period (p < 0.001). ATOR displayed a more prominent decrease of PLTP activity compared to ROSU (p = 0.043), while ROSU displayed a more prominent decrease of Lp-PLA2 activity compared to ATOR (p = 0.04). Both statins effectively reduced, in a dose-dependent way, high sensitivity C-reactive protein values over time, while no effect on the levels of circulating inter cellular adhesion molecule 1 (cICAM-1) was observed.Conclusions:The effects of statin treatment extend further and beyond a mere TChol and LDL cholesterol reduction, as demonstrated by the aforementioned alterations of lipoproteins, enzymes and lipid transfer proteins involved in lipoprotein metabolism and pro-atherogenic and inflammatory molecules. ROSU and ATOR displayed a similar pattern of effect on lipid metabolism with discrete differences in the magnitude of this effect in certain variables. Despite the limitations of small population size and lack of clinical end points, reported data provide an insight for the possible pathophysiological mechanisms implicated in the effect of increasing dosages of different statin treatments.

Probucol therapy overcomes the reproductive defect in CTP: phosphocholine cytidylyltransferase β2 knockout mice

The synthesis of phosphatidylcholine (PtdCho), the major phospholipid in mammalian cells, is regulated by the CTP:phosphocholine cytidylyltransferase (CCT). Loss of the CCTβ2 isoform expression in mice results in gonadal dysfunction. CCTβ2−/− females exhibit ovarian tissue disorganization with progressive loss of follicle formation and oocyte maturation. Ultrastructure revealed a disrupted association between ova and granulosa cells and disorganized Golgi apparati in oocytes of CCTβ2−/− mice. Probucol is a cholesterol-lowering agent that stimulates the uptake and retention of lipids carried by lipoproteins in peripheral tissues. Probucol therapy significantly lowered both serum cholesterol and PtdCho levels. Probucol therapy increased fertility in the CCTβ2−/− females 100%, although it did not completely correct the phenotype, the morphological abnormalities in the knockout ovaries or itself stimulate CCT activity directly. These data indicated that a deficiency in de novo PtdCho synthesis could be complemented by altering the metabolism of serum lipoproteins, an alternative source for cellular phospholipid.

Royal Jelly Supplementation Improves Lipoprotein Metabolism in Humans

Royal jelly (RJ) has several physiological effects and is widely used in commercial medical products and health foods. We examined the effects of RJ supplementation on serum lipoprotein metabolism in humans. Fifteen volunteers were divided into an RJ intake group (n=7) and a control group (n=8). The RJ group took 6 g per day for 4 wk. Their serum total cholesterol (TC) and serum low-density lipoprotein (LDL) decreased significantly compared with those of the control group (p<0.05). There were no significant differences in serum high-density lipoprotein (HDL) or triglyceride concentrations. Moreover, the relationship between the serum cholesterol and lipoprotein levels was investigated. Among the lipoprotein fractions, small very-low-density lipoprotein was decreased (p<0.05) after RJ intake. Our results suggest that dietary RJ decreases TC and LDL by lowering small VLDL levels.

Lipoproteins in inflammation and sepsis. II. Clinical aspects

Systemic inflammation and sepsis are accompanied by severe metabolic alterations, including insulin resistance together with increased levels of triglycerides (TGs) and decreases in high- and low-density lipoproteins. Clinical studies have clearly established a link between lipid metabolism and systemic inflammation. Lipoproteins were shown to neutralize LPS and to exert direct anti-inflammatory actions. High- and low-density lipoproteins are thus thought to be important regulators of the host immune response during endotoxemia, which may also have the potential of improving the care of patients with Gram-negative sepsis. Nutritional lipids supplied during critical illness have been shown to modulate the host response to inflammation. In particular, inclusion of omega-3 fatty acids seems to have beneficial effects on cellular immunity and helps to maintain the balance between pro- and anti-inflammatory cytokines thereby preventing hyperinflammatory complications. In addition to improvements in the profile of lipid mediators generated, omega-3 fatty acids act as activating ligands of peroxisome proliferator-activated receptors and directly inhibit nuclear factor kappaB mediated proinflammatory signaling. We present an overview on the alterations in the metabolism of serum lipoproteins during sepsis and present data from clinical studies and discuss the significance of nutritional lipids and their role in immunomodulation with special emphasis on omega-3 fatty acids.

Effect of soya protein on serum lipid profile and lipoprotein concentrations in patients undergoing hypercholesterolaemic haemodialysis

Clinical trials have shown that soya protein reduces the concentrations of some atherogenic lipids in subjects with normal renal function. The present study examined the effects of soya protein on serum lipid concentrations and lipoprotein metabolism in patients on hypercholesterolaemic haemodialysis. Twenty-six hypercholesterolaemic (total cholesterol > or =6.21 mmol/l) patients on haemodialysis were studied in a randomized, double-blind, placebo-controlled clinical trial. After a 4-week run-in phase, the subjects were randomly assigned to two groups. Isolated soya protein or milk protein 30 g was consumed daily as a beverage at breakfast or post-dialysis for 12 weeks. Soya protein substitution resulted in significant reductions in total cholesterol (17.2 (sd 8.9 )%), LDL-cholesterol (15.3 (sd 12.5 )%), apo B (14.6 (sd 12.1 )%) and insulin (23.8 (sd 18.7) %) concentrations. There were no significant changes in HDL-cholesterol or apo A-I. These results indicate that replacing part of the daily protein intake with soya protein has a beneficial effect on atherogenic lipids and favourably affects lipoprotein metabolism in hypercholesterolaemic patients undergoing haemodialysis.

Novel truncated isoforms of constitutive serum amyloid A detected by MALDI mass spectrometry

The main focus of the serum amyloid A (SAA) family has been on the acute phase isoforms. However, the constitutive isoform (SAA4) may have a strong effect on the metabolism of human serum lipoproteins. In this study, the SAA4 protein was examined in the high-density lipoprotein fraction of both healthy and diseased individuals. Novel isoforms of SAA4 were detected using ultracentrifugation combined with solid-phase extraction and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Three truncated isoforms were identified as well as two glycosylated isoforms. Patterns of isoform distribution may be significant for assessment of cardiovascular risk as well as direction of patient treatment.

Effects of dietary fats on senile amyloidosis in SAMP1 mice

The SAMP1 mouse (SAMP1@Umz) is an animal model of senile amyloidosis, with apolipoprotein A-II amyloid fibril (AApoA-II) deposits. This study was undertaken to investigate the effects of dietary fats on AApoA-II deposits in SAMP1 mice, when purified diets containing 4% fat as butter, safflower oil or fish oil were fed to male mice for 14 and 26 weeks. Severe AApoA-II deposits were observed in the fish oil group as compared with the butter and safflower oil groups. Serum apolipoprotein A-II levels were significantly lower in the mice on the fish oil diet than those mice fed the butter or safflower oil diets. The mice fed with fish oil had a significantly smaller high density lipoprotein (HDL) particle size than those fed butter or safflower oil. On the other hand, there were dramatic changes in the fatty acid composition of the HDL particles in the mice fed the fish oil diet as compared with the HDLs of mice fed the safflower oil diet. These findings suggest that dietary fats differ in their effects on serum lipoprotein metabolism, and that dietary lipids may modulate amyloid deposition in SAMP1 mice.

달리기와 근저항 복합운동이 20대 비만여성의 지질, 지단백 및 아포지단백 대사에 미치는 영향

The purpose of this study was to investigate the changes of lipid, lipoprotein and apolipoprotein concentration after 12-week combined aerobic exercise and resistance training. Subjects were composed of 6 obese women in their twenties. The training program was separated indoor running and muscular resistance training. The indoor running was composed of 60% HRmax, 20 minutes per day, 4 days per week, and the method of muscular resistance training during 12 weeks was established to practice the training of 3 sets through repeated frequency of 30-35 times with the loading of the load was gradually increased by measuring 1RM every 2 weeks. In the changes of serum lipid, lipoprotein and apolipoprotein concentration, T-C, TG, LDL-C, VLDL-C, T-C/HDL, LDL/HDL, Apo-B, Apo C-Ⅲ, Apo-B/Apo A-Ⅰ, AI, and Lipase showed significantly decrease as a result of 12-week combined exercise training, whereas FFA, HDL-C, Apo A-Ⅰ, A-Ⅱ and Apo C-Ⅱ revealed significantly increase after combined exercise training. In this result, it could be suggested that 12-week combined aerobic exercise and resistance training demonstrated positive effects to the changes of serum lipid, lipoprotein and apolipoprotein metabolism. Therefore, it is maybe thought that combined training program was ideal exercise type for the obese female.

Effects of hormone replacement therapy and hepatic lipase polymorphism on serum lipid profiles in postmenopausal Japanese women.

The purpose of this study was to evaluate the relationships among hepatic lipase (HL) polymorphism, serum lipids, lipoproteins, and remnant-like particle cholesterol (RLP-C) and to determine the effects of hormone replacement therapy (HRT). We assessed the HL polymorphism in 209 postmenopausal Japanese women. Levels of serum total cholesterol, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, triglycerides, apolipoprotein (Apo) AI, Apo B, Apo E, Apo CII, Apo CIII, and RLP-C were measured before and after 3 months of HRT. The frequency of each genotype was 32% for -514 C/C, 41% for C/T, and 27% for T/T. Subjects with the C/T and T/T genotypes had higher levels of HDL cholesterol and Apo AI than those with the C/C genotype. Those with the T/T genotype had higher levels of RLP-C than those with the C/C or C/T genotype. Serum total cholesterol, LDL cholesterol, Apo B, Apo E, and Apo CII were decreased, and HDL cholesterol and Apo AI were increased significantly in all genotypes after 3 months of HRT. There were no differences in these changes with genotype. The HL polymorphism was associated with higher levels of HDL cholesterol, Apo AI, and RLP-C, and the HL gene variation may contribute to HL activity and affect serum lipoprotein metabolism. Effects of HRT on serum lipids, lipoproteins, and remnant lipoprotein metabolism were unaffected by the HL polymorphism.

Apolipoprotein E Polymorphism in a Healthy Lebanese Population

Objective: The gene for apolipoprotein (apo) E, which modulates serum lipoprotein metabolism and concentration, is polymorphic with three major alleles, E2, E3, and E4, and a corresponding six apo E genotypes, E2/E2, E3/E2, E3/E3, E4/E2, E4/E3, and E4/E4. Due to its clinical importance in regulating lipid transport and redistribution, and coupled with the association of certain apo E alleles with metabolic disorders, we investigated apo E genotype in 155 healthy Lebanese individuals of both sexes, aged 5–77, by PCR/Cfo I restriction analysis. Methods: Total genomic DNA was extracted from the peripheral blood of study subjects, and apo E genomic sequence was amplified by PCR using one set of primers defining a conserved region of apo E gene. Apo E genotype was determined by the digestion of the PCR products with Cfo I, followed by agarose gel electrophoresis. Results: Among the genotypes obtained the most prevalent were: E3/E3 (120/155; 77.42%), E2/E3 (20/155; 12.90%), E3/E4 (13/155; 8.39%), and E2/E4 (2/155; 1.29%). None of the homozygous E2/E2 or E4/E4 genotypes were detected. Furthermore, there was no difference in apo E genotype distribution with regard to age or sex, which is in accordance with the reports for other study populations. Conclusions: The finding that apo E3/E3 is the most significant genotype in healthy Lebanese is similar to what was described for Caucasian populations. Further studies are required to establish the prevalence of homozygous E2/E2 and E4/E4.

Interactions among Lp(a) phenotypes, Lp(a) concentrations and lipoprotein response to fat-modified diets

Lipoprotein(a) (Lp(a)), an LDL-like particle containing apo(a), a highly glycosylated protein, is a significant genetic risk factor for coronary heart disease (CHD). Lp(a) phenotypes are characterized into single-band and double-band phenotypes according to electrophoretic mobility compared to that of apo B-100. The first goal was to assess whether Lp(a) phenotype influences the concentrations and metabolism of other serum lipoproteins. A second focus was to evaluate the effect on Lp(a) concentrations of substituting medium chain saturated fat for a polyunsaturated, baseline diet. In this two-way cross-over study 18 females are a baseline, polyunsaturated fat diet ( Poly Sat en% ratio = 10.5 11.9 ) for 1 week, and then a high saturated fat diet for 4 weeks ( Poly Sat en% ratio = 3.4 19.8 ) providing either 14 energy % medium chain triglycerides (MCT) 8:0 + 10:0 or 12:0, whereas monounsaturated fat was held constant. Subjects with double-band Lp(a) phenotypes had higher ( P = 0.000) Lp(a) levels on the baseline diet compared to single-band phenotypes. Both diets decreased serum Lp(a) concentration about 30% ( P < 0.05) but raised serum LDL-C about 11%. On the baseline diet, Lp(a) polymorphism did not affect serum LDL-cholesterol levels or receptor-mediated uptake and degradation of LDL. In a two-way ANOVA 8:0 + 10:0 and 12:0 had significantly different effects on change in serum HDL-C concentrations and LDL receptor activity in MNC, but Lp(a) polymorphism had no effect on the variables measured in this study. These results suggest that the response of LDL and Lp(a) levels to the two saturated fat diets were independent of each other. Lp(a) polymorphism did not seem to influence LDL metabolism.

The association of serum nonesterified fatty acids and cholesterol, management and feeding practices with peripartum disease in dairy cows

A prospective study was conducted to determine the relationship of serum nonesterified fatty acids (NEFA) and cholesterol concentrations and herd management practices to the occurrence of metritis, mastitis and retained placenta in Holstein cows in Michigan. Serum samples were collected once prepartum and once postpartum from 257 cows. Animals were under observation for disease occurrence from the date of calving until 3 months postpartum. Metabolic variables used were: (1) prepartum only; (2) postpartum only; (3) the NEFA/cholesterol ratio for both preand postpartum samples. Management variables included maternity management, feed management, and factors such as season and parity. Multivariable logistic models with random-effect terms to account for the herd effect were used for data analysis. Results showed that: (1) metabolic events associated with energy insufficiency—increased fat mobilization and serum lipoprotein metabolism—were related to increased risk of metritis and retained placenta; (2) higher energy consumption during the last weeks of the dry period might reduce disease risk at parturition; (3) serum NEFA and cholesterol concentrations have potential as indicators of disease risk in dairy cows.