Association of apolipoprotein B gene variants with plasma apoB and low density lipoprotein (LDL) cholesterol levels

1992 ◽  
Vol 88 (4) ◽  
pp. 463-470 ◽  
Author(s):  
Samir S. Deeb ◽  
R. Alan Failor ◽  
B. Greg Brown ◽  
John D. Brunzell ◽  
John J. Albers ◽  
...  
Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Joseph L Evans ◽  
Harold Bays ◽  
Kevin C Maki ◽  
Mal Evans ◽  
Veronique Maquet ◽  
...  

Oxidized low-density lipoprotein (OxLDL) is believed to play a role in the progression of atherosclerotic coronary heart disease (CHD) and the development of diabetes complications. This randomized, double-blind, placebo-controlled study of a novel insoluble fiber derived from the mycelium Aspergillus niger , chitin-glucan (CG) (ARTINIA™), evaluated 135 patients with fasting LDL-cholesterol 130-189.9 mg/dl and fasting glucose <=125 mg/dl. Participants were randomly assigned to receive CG (4.5 g/day; n=34), CG (1.5 g/day; n=33), CG (1.5 g/day) plus olive extract (n=33), or matching placebo (n=35) for 6 weeks. The primary outcome measure was the between-group difference in OxLDL. Secondary outcome measurements included effects upon lipid, glucose, insulin, and F2-isoprostane levels. After 6 weeks, CG 4.5 g/day (CG-4.5) significantly reduced mean OxLDL 3.8 U/L compared to baseline (58.0 U/L vs 61.8 U/L, respectively; P =0.006), and reduced OxLDL 4.97 U/L compared to placebo (P=<0.05). Other treatment groups generally had no significant effect upon OxLDL. CG treatment groups reduced LDL-cholesterol levels 3.2–;6.5% compared to placebo (P<0.05). In this study population without diabetes mellitus or elevated glucose levels, CG did not significantly affect high density lipoprotein cholesterol, triglycerides, glucose, insulin, F2-isoprostanes, or the homeostasis model assessment of insulin resistance. Treatments were well tolerated and with adverse experiences comparable to placebo. These results suggest that chitin-glucan, a novel insoluble fiber, may significantly reduce OxLDL and LDL-cholesterol levels, which may have therapeutic implications for patients at risk for CHD or other diabetes complications.


2018 ◽  
Author(s):  
Johannes Kettunen ◽  
Michael V. Holmes ◽  
Elias Allara ◽  
Olga Anufrieva ◽  
Pauli Ohukainen ◽  
...  

AbstractBackgroundCETP inhibition reduces vascular event rates but confusion surrounds its low-density lipoprotein (LDL)-cholesterol effects. We sought to clarify associations of genetic inhibition of CETP on detailed lipoproteins.Methods and ResultsWe used variants associated withCETP(rs247617) andHMGCR(rs12916) expression in 62,400 Europeans with detailed lipoprotein profiling from nuclear magnetic resonance spectroscopy. Genetic associations were scaled to 10% lower risk of coronary heart disease (CHD). Associations of lipoprotein measures with risk of incident CHD in three population-based cohorts (770 cases) were examined.CETPandHMGCRhad near-identical associations with LDL-cholesterol concentration estimated by Friedewald-equation.HMGCRhad a relatively consistent effect on cholesterol concentrations across all apolipoprotein B-containing lipoproteins.CETPhad stronger effects on remnant and very-low-density lipoprotein cholesterol but no effect on cholesterol concentrations in LDL defined by particle size (diameter 18–26 nm) (-0.02SD 95%CI: -0.10, 0.05 forCETPversus -0.24SD, 95%CI -0.30, -0.18 forHMGCR).CETPhad profound effects on lipid compositions of lipoproteins, with strong reductions in the triglyceride content of all highdensity lipoprotein (HDL) particles. These alterations in triglyceride composition within HDL subclasses were observationally associated with risk of CHD, independently of total cholesterol and triglycerides (strongest HR per 1-SD higher triglyceride composition in very-large HDL 1.35; 95%CI: 1.18, 1.54).ConclusionCETP inhibition does not affect size-specific LDL cholesterol but may lower CHD risk by lowering cholesterol in other apolipoprotein-B containing lipoproteins and lowering triglyceride content of HDL particles. Conventional composite lipid assays may mask heterogeneous effects of lipid-altering therapies.


1991 ◽  
Vol 37 (2) ◽  
pp. 296-300
Author(s):  
G Huet ◽  
M C Dieu ◽  
A Martin ◽  
G Grard ◽  
J M Bard ◽  
...  

Abstract We describe a disorder in which low-density lipoprotein (LDL)-cholesterol and apolipoprotein B are in low concentration (0.47 mmol/L and 0.28 g/L, respectively) and chylomicrons are still present in plasma after an 18-h fast. The d less than 1.006 fraction was isolated by flotation ultracentrifugation and the apolipoproteins were analyzed by electrophoresis, immunoblotting with anti-apolipoprotein B-100 antiserum, and isoelectric focusing. In the d less than 1.006 fraction of the fasting serum, we found an apolipoprotein B form with the same apparent molecular mass as apolipoprotein B-48 and similar in amount to apolipoprotein B-100 (respective percentages, 46% and 54%). The monosialylated form of the apolipoprotein C-III was severely decreased. After an oral fat load, the repartition of the two species of apolipoprotein B did not change greatly (respective percentages, 60% and 40%), and the concentration of serum triglyceride increased only from 1.20 to 1.65 mmol/L.


Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2843
Author(s):  
Małgorzata Jamka ◽  
Nina Kaczmarek ◽  
Edyta Mądry ◽  
Patrycja Krzyżanowska-Jankowska ◽  
Joanna Bajerska ◽  
...  

This study aimed to evaluate the association of genetic variants in lactoferrin (LTF) metabolism-related genes with the prevalence of metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). In total, 161 MHO and 291 MUHO subjects were recruited to the study. The following polymorphisms were genotyped: low-density lipoprotein receptor-related protein (LRP) 2 rs2544390, LRP1 rs4759277, LRP1 rs1799986, LTF rs1126477, LTF rs2239692 and LTF rs1126478. We found significant differences in the genotype frequencies of LTF rs2239692 between MHO and MUHO subjects, with the CT variant associated with lower odds of developing metabolic syndrome than the TT variant. In the total population, significant differences in body weight and waist circumference (WC) were identified between LTF rs1126477 gene variants. A similar association with WC was observed in MUHO subjects, while significant differences in body mass index and low-density lipoprotein cholesterol levels were discovered between LTF rs1126477 gene variants in MHO subjects. Besides, there were significant differences in diastolic blood pressure between LRP1 rs1799986 gene variants in MUHO subjects, as well as in WC and high-density lipoprotein cholesterol levels between LRP1 rs4759277 gene variants in MHO subjects. In conclusion, selected lactoferrin and lactoferrin receptor-related gene variants may be associated with the prevalence of metabolically healthy or metabolically unhealthy obesity.


2018 ◽  
Vol 17 (6) ◽  
pp. 563-570 ◽  
Author(s):  
Laila A Hopstock ◽  
Anne Elise Eggen ◽  
Maja-Lisa Løchen ◽  
Ellisiv B Mathiesen ◽  
Inger Njølstad ◽  
...  

Background: Secondary prevention guidelines after myocardial infarction (MI) are gender neutral, but underutilisation of treatment in women has been reported. Design: We investigated the change in total and low-density lipoprotein (LDL) cholesterol levels and lipid-lowering drug (LLD) use after first-ever MI in a population-based study. Methods: We followed 10,005 participants (54% women) attending the Tromsø Study 1994–1995 and 8483 participants (55% women) attending the Tromsø Study 2007–2008 for first-ever MI up to their participation in 2007–2008 and 2015–2016, respectively. We used linear and logistic regression models to investigate sex differences in change in lipid levels. Results: A total of 395 (MI cohort I) and 132 participants (MI cohort II) had a first-ever MI during 1994–2008 and 2007–2013, respectively. Mean change in total cholesterol was −2.34 mmol/L (SD 1.15) in MI cohort I, and in LDL cholesterol was −1.63 mmol/L (SD 1.12) in MI cohort II. Men had a larger decrease in lipid levels compared to women: the linear regression coefficient for change was −0.33 (95% confidence interval [CI] −0.51 to −0.14) for total cholesterol and −0.21 (95% CI −0.37 to −0.04) for LDL cholesterol, adjusted for baseline lipid value, age and cohort. Men had 73% higher odds (95% CI 1.15−2.61) of treatment target achievement compared to women, adjusted for baseline lipid value, age and cohort. LLD use was reported in 85% of women and 92% of men in MI cohort I, and 80% in women and 89% in men in MI cohort II. Conclusions: Compared to men, women had significantly less decrease in lipid levels after MI, and a smaller proportion of women achieved the treatment target.


Scientifica ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-21 ◽  
Author(s):  
Nicola Ferri

The identification of the HMG-CoA reductase inhibitors, statins, has represented a dramatic innovation of the pharmacological modulation of hypercholesterolemia and associated cardiovascular diseases. However, not all patients receiving statins achieve guideline-recommended low density lipoprotein (LDL) cholesterol goals, particularly those at high risk. There remains, therefore, an unmet medical need to develop additional well-tolerated and effective agents to lower LDL cholesterol levels. The discovery of proprotein convertase subtilisin/kexin type 9 (PCSK9), a secretory protein that posttranscriptionally regulates levels of low density lipoprotein receptor (LDLR) by inducing its degradation, has opened a new era of pharmacological modulation of cholesterol homeostasis. This paper summarizes the current knowledge of the basic molecular mechanism underlying the regulatory effect of LDLR expression by PCSK9 obtained fromin vitrocell-cultured studies and the analysis of the crystal structure of PCSK9. It also describes the epidemiological and experimental evidences of the regulatory effect of PCSK9 on LDL cholesterol levels and cardiovascular diseases and summarizes the different pharmacological approaches under development for inhibiting PCSK9 expression, processing, and the interaction with LDLR.


2017 ◽  
Vol 4 (1) ◽  
pp. 39-44
Author(s):  
Ni Made Restina Juliani ◽  
I Putu Oka Dharmawan ◽  
Putu Ayu Parwati

Introduction: Low Density Lipoprotein (LDL) is a type of low-density lipoprotein and the most widely transported cholesterol in the body. Increased levels of LDL in the body can be affected by genetics, age, gender, obesity, physical activity, lifestyle, drug consumption and smoking. Substances in a cigarette can cause an increase of LDL levels. Increased of LDL cholesterol levels can cause Coronary Heart Disease (CHD). The purpose of this research is to know the description of Low Density Lipoprotein (LDL) levels on smoker and non-smoker adolescent in Buyan Hamlet, Pancasari Village, Sukasada District, Buleleng Bali. Method: The type of this research is descriptive. This research was conducted in April-May 2017, which used fasting blood samples of 42 respondents. Result: From the average result of LDL level in smoker adolescent that is 134,91 mg/dL higher than the average of LDL level in non-smoker adolescent that is 74,90 mg/dL. The result of LDL cholesterol levels was determined by 21 smoker adolescent respondents with the close to optimal category (100-129 mg/dL) as many as 9 people (42,8%), and 12 people (57,3%) with worry category (130-159 mg/dL). Whereas in 21 non-smoker adolescent respondents obtained  result of LDL cholesterol level test with optimal category (<100 mg/dL) counted 18 people (87,71%) and 3 person (14,30%) with close to optimal category (100-129 mg/dL). Discussion: Based on the results of this research can be concluded that in smoker adolescent obtained LDL levels with close to optimal category and worrying whereas in non-smoker adolescents obtained LDL levels in the optimal category and close to optimal.


1983 ◽  
Vol 21 (19) ◽  
pp. 75-76

Bezafibrate (Bezalip - MCP), an analogue of clofibrate (Atromid-S), has been marketed in the UK for two years. Like clofibrate 1 it lowers both triglyceride and total cholesterol levels in plasma. The reduction is usually in low-density lipoprotein (LDL) cholesterol, whilst high-density lipoprotein (HDL) cholesterol rises. Like other lipid-lowering drugs, it should be used only where appropriate dietary measures have failed and where the hyperlipidaemia poses a significant risk.2


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