Genetic variants in SLC22A1 are related to serum lipid levels in Mexican women

Dyslipidemia is the main risk factor for coronary artery disease and is characterized by alterations in concentrations of lipids, including low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c), and triacylglycerols. The participation of several genes in the development of dyslipidemia has been evidenced. Genetic variants in SLC22A1 have been associated with elevated cholesterol and LDL-c levels. The aim of this study was to evaluate the association between single-nucleotide polymorphisms (SNPs) in the SLC22A1 gene with atherogenic risk lipid levels in Mexican women. Anthropometric and biochemical measurements were performed, and four SNPs in SLC22A1 were genotyped by real-time polymerase chain reaction. The Hardy–Weinberg equilibrium was verified, and haplotype frequencies were calculated. We found significant differences between the allele frequencies of the SNPs analyzed with those reported in Mexico and in the world, which could be due to differences in the historical admixture of the women studied. Generalized linear models were evaluated to determine the association between genotypes and haplotypes with lipids levels. We identified a significant increase in total cholesterol and LDL-c levels in women who were carriers of the GA and AG genotypes of the polymorphisms rs628031 and rs594709, respectively, significant effect that is also shown in a dominant inheritance model. Interestingly, we identified an important relationship of the AGC-GAT haplotype with the elevation in LDL-c levels and AGA-GAT haplotype with the elevation in HDL-c levels. On the other hand, we found a strong linkage disequilibrium between the polymorphisms studied. Our results show that variants in the SLC22A1 gene influence serum levels of atherogenic risk lipids, suggesting that these variants probably affect the function of organic cation transporter-1 and therefore, on the regulation of lipid metabolism.     

8302A/C and (TTA)n polymorphisms in the HMG-CoA reductase gene may be associated with some plasma lipid metabolic phenotypes in patients with coronary heart disease

HMG-CoA reductase (HMGCR) is a rate-limiting enzyme that participates in cholesterol metabolism. Here we analyzed the 8302A/C and the (TTA)n polymorphisms in the HMGCR gene in 169 Chinese patients with coronary heart disease (CHD) and 161 age-matched controls. Results indicated that the levels of plasma VLDL and TG in patients with the AA genotype of the 8302A/C locus were significantly higher than in patients with other genotypes (P<0.05). In addition, the frequency of allele A4 of the (TTA)n locus was higher (P<0.05) and the frequency of allele A5 was lower (P=0.002) in CHD patients than in the controls. This suggests that both polymorphisms in the HMGCR gene may be associated with lipid and lipoprotein abnormalities in CHD in the Chinese.     

Hypoglycemic Effects of Crude Polysaccharide from Purslane

The effects of crude polysaccharide from Purslane (CPP) on body weight (bw), blood glucose, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), triglyceride (TG) and serum insulin levels were studied in diabetes mellitus mice. CPP treatment (200, 400 mg/kg bw) for 28 days resulted in a significant decrease in the concentrations of fasting blood glucose (FBG), TC and TG. Furthermore, CPP significantly increased the concentration of HDL-c, body weight and serum insulin level in the mice. In addition, according to acute toxicity studies and single cell gel electrophoresis analysis, CPP did not produce any physical or behavioral signs of toxicity. More significantly, our data demonstrated CPP exhibited the best effects at the dose of 400 mg/kg bw. The above results suggest that CPP can control blood glucose and modulate the metabolism of glucose and blood lipids in diabetes mellitus mice, so we conclude that CPP should be evaluated as a candidate for future studies on diabetes mellitus.     

Genetic Variation in <Emphasis Type="Italic">ABC G5/G8</Emphasis> and <Emphasis Type="Italic">NPC1L1</Emphasis> Impact Cholesterol Response to Plant Sterols in Hypercholesterolemic Men

ATP-binding cassette hetero-dimeric transporters G5 and G8 (ABCG5/G8) have been postulated to mediate intestinal cholesterol efflux, whereas Niemann-Pick C1 Like 1 (NPC1L1) protein is believed to be essential for intestinal cholesterol influx. The individual or combined genetic markers, such as single nuclear polymorphisms (SNPs), of these two transporter genes may explain inter-individual variations in plasma cholesterol response following plant sterol (PS) intervention. The present study was aimed at investigating the association between ABCG5/G8 and NPC1L1 genotype SNPs with sterol absorption and corresponding plasma concentrations. The study used a 4-week crossover design with 82 hypercholesterolemic men characterized by high vs. low basal plasma PS concentrations consuming spreads with or without 2 g/day of PS. For the ABCG8 1289 C > A (T400 K) polymorphism, the A allele carriers with high basal plasma PS concentrations demonstrated a 3.9-fold greater reduction (p < 0.05) in serum low density lipoprotein cholesterol (LDL-C) than their low basal plasma PS counterparts. For the NPC1L1 haplotype of 872 C > G (L272L) and 3929 G > A (Y1291Y), individuals carrying mutant alleles showed a 2.4-fold greater (p < 0.05) reduction in LDL-C levels, compared to wild type counterparts. Results suggest that genetic and metabolic biomarkers together may predict inter-individual lipid level responsiveness to PS-intervention, and thus could be useful in devising individualized cholesterol lowering strategies.     

EVALUATION OF A COMPOSITE BASED ON HIGH-DENSITY POLYETHYLENE FILLED WITH SURFACE-TREATED HYDROXYAPATITE

Summary  Composites properties are directly related to the degree of interaction between the plastic matrix and the inorganic filler. In the present work, the improvement of the composite’s properties by means of the addition of surface-treated and untreated hydroxyapatite (STHA and HA, respectively) was studied. An ethylene-acrylic acid copolymer was melt blended with high-density polyethylene and HA (HDPE/HA/EA). A surface treatment was performed using an ethylene-acrylic acid (EA) copolymer for STHA₁ and acrylic acid (AA) for STHA₂. High-density polyethylene (HDPE) was also tested. STHA₁ and STHA₂ composites exhibited Young’s modulus values (556 and 558 MPa, respectively) 22 % higher than that of HDPE/HA (455 MPa) and 8 % higher than that of HDPE/HA/EA (520 MPa). Additionally, STHA composites showed both yield stress and strain (σ_STHA1= 23 MPa; ε_STHA1= 9 %; σ_STHA2= 22 MPa; ε_STHA2= 10 %) having a remarkably different behavior from that of the HA composites, which showed no yielding at all. TEM micrographs showed better filler dispersion when surface treatment was applied to HA. Yet, the presence of EA copolymer exhibited a poorer thermal stability. The crystallinity degree as well as the crystallization and melting temperatures showed no significant variation. Regarding in vitro evaluation, composites with HA and EA copolymer proved to have better cell adhesion at early stages. The results of the STHA composites could be attributed to the electrostatic interactions taking place between the ethylene-acrylic acid copolymer and the polar groups of the HA.     

Effect of liposome-encapsulated hemoglobin on triglyceride, total cholesterol, low-density lipoprotein, and high-density lipoprotein cholesterol measurements

The present study investigated the effect of liposome-encapsulated hemoglobin (LEH), an experimental oxygen-carrying resuscitation fluid, on triglyceride, total cholesterol, and low density lipoprotein (LDL), and high density lipoprotein (HDL) cholesterol measurements. In vivo, the intravenous infusion of LEH (5.6 mL/kg, n=6) elevated serum triglycerides (+92% vs. baseline, P<.05), total cholesterol (+25% vs. baseline, P<.01), LDL cholesterol (+72% vs. baseline, P<.01) and had no effect on serum HDL cholesterol. In addition, LEH did not alter the elevation in serum triglycerides (+302% vs. baseline, P<.01) and LDL cholesterol (+86% vs. baseline, P<.01) induced by lipopolysaccharide (3.6 mg/kg, i.v., n=6). Ex vivo, measurements of triglycerides and total cholesterol as well as LDL and HDL cholesterol in whole blood from naive rats were not changed by the addition of LEH (0–50%, n=6). In vitro, the addition of a fixed concentration of LEH (50%, n=6) to varying concentrations of cholesterol solution (0–50%), or vice versa, had no effect on cholesterol determination. It is therefore concluded that LEH only minimally affects serum levels of triglycerides, total cholesterol, LDL cholesterol, and HDL cholesterol and does not interfere with their measurement.     

Dietary phospholipid alters biliary lipid composition in formula-fed piglets

Plasma cholesterol, arachidonic acid (AA, 20∶4n−6), and docosahexaenoic acid (DHA, 22∶6n−3) are higher in breast-fed infants than in infants fed formula without cholesterol, AA, or DHA. This study investigated differences in plasma, hepatic, and bile lipids and phospholipid fatty acids, and expression of hepatic proteins involved in sterol metabolism that result from feeding formula with cholesterol with egg phospholipid to provide AA and DHA. For this study, three groups of piglets were evaluated: piglets fed formula with 0.65 mmol/L cholesterol, the same formula with 0.8% AA and 0.2% DHA from egg phospholipid, and piglets fed sow milk. Piglets fed the formula with phospholipid AA and DHA had higher plasma high density lipoprotein, but not apoprotein (apo) B cholesterol or triglyceride; higher bile acid and phospholipid concentrations in bile; and higher liver and bile phospholipid AA and DHA than piglets fed formula without AA and DHA (P<0.05). Hydroxy methylglutaryl (HMG)-CoA reductase and 7-α-hydroxylase, the rate-limiting enzymes of cholesterol and bile acid synthesis, respectively, and low density lipoprotein receptor mRNA levels were not different between piglets fed formula without and with phospholipid AA and DHA, but HMG-CoA reductase and 7α-hydroxylase mRNA were higher, and plasma apo B containing lipoprotein cholesterol was lower in all piglets fed formula than in piglets fed milk. These studies show that supplementing formula with AA and DHA from egg phospholipid alters bile metabolism by increasing the bile AA and DHA, and bile acid and phospholipid.     

Common Variants of <Emphasis Type="Italic">ABCB4</Emphasis> and <Emphasis Type="Italic">ABCB11</Emphasis> and Plasma Lipid Levels: A Study in Sib Pairs with Gallstones,and Controls

Most epidemiological surveys have confirmed the association of low HDL-cholesterol and high triglyceride levels with cholesterol gallstones. Our objective was to analyze the relationship between plasma lipid levels and common polymorphisms of ABCB11 (encoding the bile salt export pump, BSEP) and ABCB4 (encoding the phospholipid transporter into bile, MDR3) genes. Plasma lipids were measured in 108 index patients of sib pairs with gallstones and in 260 controls. Using PCR-based assays with 5′-nuclease and fluorescence detection (TaqMan), the ABCB11 coding SNP p.A444V and four haplotype-tagging SNPs covering the ABCB4 gene (c.504C > T, c.711T > A, p.R652G, rs31653 in intron 26) were genotyped. Plasma lipids were compared in carriers of the common versus rare allele of these polymorphisms using Student’s t test and Pearson’s correlation. BMI and triglyceride levels were higher and HDL-cholesterol levels were lower in affected siblings than in controls. Among cases, triglyceride and cholesterol levels were higher in carriers of the common versus rare (hetero/homozygous carriers) allele of the SNPs p.A444V of ABCB11 and C.504C > T of ABCB4. HDL-cholesterol was lower in carriers of the common allele of rs31653. In controls, significant differences of cholesterol and HDL-cholesterol levels were found in carriers of ABCB4 polymorphisms. Our results do not support the hypothesis of a link between ABCB4 and ABCB11 polymorphisms, lithogenic dyslipidemia, and gallstone risk.     

Adsorptive removal of tetracycline from water using Fe (III)-functionalized carbonized humic acid

Humic acid (HA) was carbonized at 300, 400 and 500 ℃ and then functionalized with 1 wt%-12 wt% Fe(III) respectively [CHA300/400/500-Fe(III)]. Adsorption of such Fe(III)-functionalized carbonized HA as adsorbents to aqueous tetracycline (TC: 25 mg·L^-1) was studied. The adsorption equilibrium time for CHA400-Fe(III) to TC was 6 h faster and the adsorption removal efficiency (R_e) was two times higher than that of HA/CHA. The adsorption R e of CHA400-Fe(III) loaded 10% iron [CHA400-(10%)Fe(III)] to TC could reach 99.8% at 8 h and still kept 80.6% after 8 cycles. The adsorption kinetics were well fitted to the pseudo-second-order equation and the adsorption isotherms could be well delineated via Langmuir equations(R² > 0.99), indicating that the homogeneous chemical adsorption of TC occurred on the adsorbents. The main adsorption mechanisms of TC were complexation Fe(III) and hydrophobic distribution. Electropositive and electronegative repulsion between TC and CHA400-(10%)Fe(III) at lowly pH(2) and highly pH(8-10) respectively, leaded to the relatively low adsorption capacity and more notable influence of ion concentration. When the pH was between 4 and 8, TC mainly existed in neutral molecules (TCH₂), so the influence of ion concentration was not obvious. The dynamic adsorption results showed that the CHA400-(10%)Fe(III) could continuously treat about 2.4 L TC(27 mg·L^-1) wastewater with the effluent concentration as low as 0.068 mg·L^-1. Our study suggested a broad application prospect of a new, effective, lowcost and environment-friendly adsorbent CHA400-(10%)Fe(III) for treatment of low-concentration TC polluted wastewater.     

Effects of dietary triglyceride on the properties and lipid composition of plasma lipoproteins: Acute experiments in rats fed safflower oil

Male rats were administered 1.5 ml safflower oil by gastric intubation 0, 4, and 8 hr after a 16 hr fast. Plasma, liver, and adipose tissue were collected 16 hr after the last fatty meal. Rats fasted for 16 hr served as controls. Following fat feeding, the fatty acid composition of the very low density lipoprotein, triglyceride, and hepatic triglyceride were similar, as were the percentages of 18:2 in the very low density lipoprotein and hepatic cholesteryl esters. The phospholipids of liver and plasma lipoproteins were similar in the control groups, except that more 16:0 was present in the plasma lipoproteins. After fat feeding, the plasma lipoproein phospholipids were enriched with 18:2 more than were the hepatic phospholipids. Furthermore, the percentage of 18:2 in phospholipid was much less than in triglyceride or cholesteryl esters. Clearly, esterified lipids of liver and plasma lipoproteins (very low density lipoprotein, low density lipoprotein, and high density lipoprotein), and to a lesser extent, adipose tissue, were enriched with 18:2 derived from dietary triglyceride fatty acid even 16 hr after the terminal meal. A major proportion of the very low density lipoprotein isolated by ultracentrifugation in zonal rotors from plasma of fat fed animals had a faster rate-zonal mobility than did the very low density lipoprotein isolated from plasma of control animals. The very low density lipoprotein isolated from plasma of fat fed rats contained fewer moles of phospholipids, cholesterol, and cholesteryl esters, relative to triglyceride than did the very low density lipoprotein from plasma of animals not receiving safflower oil. The molar ratio triglyceride:phospholipid:cholesterol:cholesterol esters in the very low denity lipoprotein was 100:42.0:22.1:44.5 in the control group and 100:35.4:17.8:19.5 in the fat fed animals. It is postulated that an important biochemical mechanism by which dietary triglyceride fatty acids consumed by the animal over a long period of time alter plasma concentrations of triglyceride, phospholipids, and cholesterol esters is the directive influence of plasma free fatty acid, derived from dietary triglyceride, on the secretion of very low density lipoprotein lipids by the liver.