Relación de los niveles plasmáticos de homocisteína y apolipoproteína b-100 con el riesgo cardiovascular / Relationship of plasma levels of homocysteine and apolipoprotein b-100 with cardiovascular risk

INTRODUCCION: las enfermedades cardiovasculares son responsables del 31% de la mortalidad mundial, existen parámetros como la homocisteína y la Apolipoproteína B-100 que podrían tener utilidad en la predicción del riesgo. OBJETIVO: relacionar los niveles plasmáticos de Homocisteína y Apolipoproteína B-100 con el riesgo cardiovascular en pacientes que acuden a consulta externa del Hospital Univalle, durante julio-agosto del 2018 METODOLOGIA: el presente estudio es no experimental observacional, tipo prospectivo, transversal, con un enfoque de análisis positivista cuantitativo, con un universo de (N=133) que se redujo a una unidad de análisis de 81, que cumplieron con los criterios de inclusión y exclusión con un 6.83% de error máximo aceptable. RESULTADOS: el 52% de los pacientes fueron mujeres. La edad media de fue de 49,8 (Rango 25 a 83), el grupo etario predominante fueron los adultos mayores. Según el IMC los sujetos de estudio presentan sobre peso (n=31) y grado de obesidad 1 (n=24) más frecuentemente. Los niveles plasmáticos elevados de Apolipoproteína B en ambos sexos no muestran una diferencia significativa, mientras en que los de homocisteína la diferencia fue de 8:1. Se constato que los niveles séricos de la Apolipoproteína B-100 tienen una sensibilidad y especificidad bajas del 19.40% y 28.42%, mientas los de la homocisteína fueron del 14.29% y 27.27% respectivamente en comparación con la técnica convencional. CONCLUSIONES: los niveles plasmáticos de homocisteína y Apolipoproteína B-100 no son parámetros predictores de padecer riesgo cardiovascular

INTRODUCTION: cardiovascular diseases are responsible for 31% of world mortality, there are parameters such as homocysteine and Apolipoprotein B-100 that could be useful in predicting risk. OBJECTIVE: to relate the plasma levels of Homocysteine and Apolipoprotein B-100 with cardiovascular risk in patients who attend the outpatient clinic of the Univalle Hospital, during July-August 2018. METHODOLOGY: this study is non-experimental, observational, prospective, cross-sectional, with a quantitative positivist analysis approach, with a universe of (N=133) that was reduced to an analysis unit of 81, who met the inclusion criteria. and exclusion with a 6.83% maximum acceptable error. RESULTS: 52% of the patients were women. The mean age was 49.8 (range 25 to 83), the predominant age group was the elderly. According to the BMI, the study subjects are overweight (n=31) and obesity grade 1 (n=24) more frequently. The elevated plasmatic levels of Apolipoprotein B in both sexes do not show a significant difference, while in those of homocysteine the difference was 8:1. It was found that the serum levels of Apolipoprotein B-100 have a low sensitivity and specificity of 19.40% and 28.42%, while those of homocysteine were 14.29% and 27.27% respectively compared to the conventional technique. CONCLUSIONS: plasma levels of homocysteine and Apolipoprotein B-100 are not predictors of cardiovascular risk.

Phenotype of definite familial hypercholesterolemia with negative genetic study in Argentina / Fenotipo de hipercolesterolemia familiar definitivo con estudio genético negativo en Argentina

Abstract Objective: Familial hypercholesterolemia (FH) is a monogenic disease, associated with variants in the LDLR, APOB and PCSK9 genes. The initial diagnosis is based on clinical criteria like the DLCN criteria. A score > 8 points qualifies the patient as "definite" for FH diagnosis. The detection of the presence of a variant in these genes allows carrying out familial cascade screening and better characterizes the patient in terms of prognosis and treatment. Methods: In the context of the FH detection program in Argentina (Da Vinci Study) 246 hypercholesterolemic patients were evaluated, 21 with DLCN score > 8 (definite diagnosis).These patients were studied with next generation sequencing to detect genetic variants, with an extended panel of 23 genes; also they were adding the large rearrangements analysis and a polygenic score of 10 SNP (single nucleotide polymorphism) related to the increase in LDL-c. Results: Of the 21 patients, 10 had variants in LDLR, 1 in APOB with APOE, 1 in LIPC plus elevated polygenic score, and 2 patients showed one deletion and one duplication in LDLR, the later with a variation in LIPA. It is highlighted that 6 of the 21 patients with a score > 8 did not show any genetic alteration. Conclusions: We can conclude that 28% of the patients with definite clinical diagnosis of FH did not show genetic alteration. The possible explanations for this result would be the presence of mutations in new genes, confusing effects of the environment over the genes, the gene-gene interactions, and finally the impossibility of detecting variants with the current available methods.

Resumen Objetivo: La hipercolesterolemia familiar (HF) es una enfermedad monogénica asociada a variantes en los genes RLDL, APOB y PCSK9. El diagnóstico inicial se basa en criterios clínicos, como el de la red de clínica de lípidos holandesa (DLCN). Un puntaje > 8 puntos califica al paciente como "definitivo" para diagnóstico de HF. La identificación de una variante en estos genes permite realizar el cribado en cascada familiar y caracterizar mejor al paciente en cuanto al pronóstico y el tratamiento. Métodos: En el marco del Programa de Detección de HF en Argentina (Estudio Da Vinci) se evaluó a 246 pacientes hipercolesterolémicos, 21 con puntaje DLCN > 8 (diagnóstico definitivo). Se estudió a estos pacientes con secuenciación de próxima generación para reconocer variantes genéticas, con un panel ampliado de 23 genes, sumado al análisis de grandes rearreglos y por último se aplicó un score poligénico de 10 SNP (polimorfismo de nucleótido único) relacionados con aumento del c-LDL. Resultados: De los 21 pacientes, 10 presentaron variantes en RLDL, uno en APOB junto a APOE, uno en LIPC más puntaje poligénico elevado, dos pacientes con una deleción y una duplicación en RLDL y este último caso con una variante en LIPA. Es destacable que 6 de los 21 pacientes con puntaje DLCN > 8 no mostraron ninguna alteración genética. Conclusiones: El 28% de los pacientes con diagnóstico clínico definitivo de HF no evidenció alteración genética. Las posibles explicaciones de este resultado serían la presencia de mutaciones en nuevos genes, los efectos confundidores del ambiente sobre los genes o la interacción gen-gen y por último la imposibilidad de detectar variantes con la metodología actual disponible.

Increased ApoB/ApoA1 ratio is associated with excess weight, body adiposity, and altered lipid profile in children / A razão ApoB/ApoA1 aumentada está associada ao excesso de peso, de adiposidade corporal e ao perfil lipídico alterado em crianças

Abstract Objective: To investigate ApoB/ApoA1 ratio and its association with cardiovascular risk factors in children. Methods: Cross-sectional study with 258 children aged 8 and 9 years old, enrolled in all urban schools in the city of Viçosa-MG. Anthropometric and body composition assessment, as well as biochemical profile of the children was performed. Socioeconomic variables and sedentary lifestyle were evaluated through a semi-structured questionnaire. Results: Many children had excess weight (35.2%), abdominal adiposity (10.5%), and body fat (15.6%), as well as increased ApoB/ApoA1 ratio (14.7%), total cholesterol (51.8%), and triglycerides (19.8%). Children with excess weight and total and central fat had a higher prevalence of having a higher ApoB/ApoA1 ratio, as well as those with atherogenic lipid profile (increased LDL-c and triglycerides and low HDL-c). A direct association was found between the number of cardiovascular risk factors and the ApoB/ApoA1 ratio (p = 0.001), regardless of age and income. Conclusion: The increased ApoB/ApoA1 ratio was associated with excess weight, body adiposity (total and central), and altered lipid profile in children. Children with a higher number of cardiovascular risk factors had higher ApoB/ApoA1 ratio, in both genders.

Resumo Objetivo: Investigar a razão ApoB/ApoA1 e sua relação com fatores de risco cardiovascular em crianças. Métodos: Estudo transversal com 258 crianças de 8 e 9 anos, matriculadas em todas as escolas urbanas de Viçosa-MG. Foi feita avaliação antropométrica, da composição corporal e bioquímica das crianças. As variáveis socioeconômicas e o sedentarismo foram avaliados por questionário semiestruturado. Resultados: Muitas crianças apresentaram excesso de peso (35,2%), de adiposidade abdominal (10,5%) e de gordura corporal (15,6%), bem como a razão ApoB/ApoA1 (14,7%), colesterol-total (51,8%) e triglicerídeos (19,8%) aumentados. Crianças com excesso de peso e de gordura total e central apresentaram maiores prevalências de maior razão ApoB/ApoA1, bem como as com perfil lipídico aterogênico (LDL-c e triglicerídeos aumentados e baixo HDL-c). Foi encontrada associação direta entre o número de fatores de risco cardiovascular e a razão ApoB/ApoA1 (p = 0,001), independente da idade e renda. Conclusão: A razão ApoB/ApoA1 aumentada esteve associada ao excesso de peso, de adiposidade corporal (total e central) e ao perfil lipídico alterado nas crianças. As crianças com maior número de fatores de risco cardiovascular apresentaram maior razão ApoB/ApoA1, em ambos os sexos.

Effects of emodin on lipid accumulation and inflammation in hepatocytes / 中国中药杂志

The aim of this study was to explore the effect of emodin on lipid accumulation and inflammation in hepatocytes. The cell morphology was observed by microscopy. LDH release was detected by the kit. Levels of intracellular lipid droplets were observed by oil red O staining. The contents of TC and TG in cells were detected by the kit. Western blot was used to determine protein expressions of FASN,SREBF2,APOB,IL-6 and p-NF-κB in hepatocytes. The results showed that the levels of L02 cell LDH were significantly increased after being treated with emodin,and the cells showed shrinkage,volume reduction,decrease in quantity with the increase of dose. Red lipid droplets were observed in L02 hepatocytes. Intracellular TC and TG contents of L02 cell increased in a concentrationdependent manner,with significant differences between medium and high-dose groups( P < 0. 05). Protein expressions of FASN,SREBF2,IL-6 and p-NF-κB were significantly higher than those of the control group,and the expression level of APOB was significantly lower than that of the control group( P<0. 05). In conclusion,emodin could induce lipid accumulation and inflammatory damage in hepatocytes in a dose-dependent manner,which in turn could damage liver cells. This process was related to the up-regulation of FASN,SREBF2,IL-6,p-NF-κB,as well as the down-regulation of the protein expression of APOB.

Genetic analysis of Iranian patients with familial hypercholesterolemia

Background: Familial hypercholesterolemia [FH] is a frequent autosomal dominant disorder of lipoprotein metabolism. This disorder is generally caused by mutations in low-density lipoprotein receptor [LDLR], apolipoprotein B 100 [APOB], and proprotein convertase subtilisin/kexin type 9 [PCSK9] genes. In the present study, we aimed at identifying the common LDLR and APOB gene mutations in an Iranian population

Methods: Eighty unrelated Iranian patients with FH entered the study, based on Simon Broome diagnostic criteria. All samples were screened for two common APOB gene mutations, including R3500Q and R3500W, by the means of ARMS-PCR and PCR- RFLP assays, respectively. In addition, exons 3, 4, 9, and 10 of LDLR gene were sequenced in all patients

Results: A novel mutation in exon 3 [C95W] and a previously described mutation in exon 4 [D139H] of LDLR gene were found. Three previously reported polymorphisms in LDLR gene as well as three novel polymorphisms were detected in the patients. However, in the studied population, no common mutations were observed in APOB gene

Conclusion: The results of our study imply that the genetic basis of FH in Iranian patients is different from other populations

A potent multivalent vaccine for modulation of immune system in atherosclerosis: an in silico approach

PURPOSE: Atherosclerosis is classically defined as an immune-mediated disease characterized by accumulation of low-density lipoprotein cholesterol over intima in medium sized and large arteries. Recent studies have demonstrated that both innate and adaptive immune responses are involved in atherosclerosis. In addition, experimental and human models have recognized many autoantigens in pathophysiology of this disease. Oxidized low-density lipoproteins, beta2 glycoprotein I (beta-2-GPI), and heat shock protein 60 (HSP60) are the best studied of them which can represent promising approach to design worthwhile vaccines for modulation of atherosclerosis. MATERIALS AND METHODS: In silico approaches are the best tools for design and evaluation of the vaccines before initiating the experimental study. In this study, we identified immunogenic epitopes of HSP60, ApoB-100, and beta-2-GPI as major antigens to construct a chimeric protein through bioinformatics tools. Additionally, we have evaluated physico-chemical properties, structures, stability, MHC binding properties, humoral and cellular immune responses, and allergenicity of this chimeric protein by means of bioinformatics tools and servers. RESULTS: Validation results indicated that 89.1% residues locate in favorite or additional allowed region of Ramachandran plot. Also, based on Ramachandran plot analysis this protein could be classified as a stable fusion protein. In addition, the epitopes in the chimeric protein had strong potential to induce both the B-cell and T-cell mediated immune responses. CONCLUSION: Our results supported that this chimeric vaccine could be effectively utilized as a multivalent vaccine for prevention and modulation of atherosclerosis.

Association between peroxisome proliferator-activated receptor and gene-gene interactions with the apolipoprotein A I/apolipoprotein B100 ratio / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between ten single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptors (PPARα, β, γ) with apolipoprotein A I/apolipoprotein B100 (ApoA I/ApoB100) ratio and the additional role of a gene-gene interactions among the 10 SNPs.</p><p><b>METHODS</b>Participants were recruited under the framework of the Prevention of Multiple Metabolic Disorders and Metabolic Syndrome in Jiangsu Province (PMMJS) cohort population survey in the urban community of Jiangsu province of China.A total of 630 subjects were randomly selected and no individual was related.Ten SNPs (rs135539, rs4253778, rs1800206, rs2016520, rs9794, rs10865710, rs1805192, rs709158, rs3856806 and rs4684847) were selected from the HapMap database,which covered PPARα, PPARβ and PPARγ. A linear regression model was used to analyze the relations between ten SNPs in the PPARs and ApoA I/ApoB100 ratio level. Mean difference and 95% CI were calculated. Interactions were explored by using the method of Generalized Multifactor Dimensionality Reduction (GMDR).</p><p><b>RESULTS</b>After adjusting for age, gender, smoking status, alcohol consumption, occupational physical activity, high-fat diet as well as low-fiber diet, both rs1800206 and rs3856806 were significantly associated with a decreased level of ApoA I/ApoB100 ratio, mean difference (95% CI) values were -1.19 (-1.88 to -0.50) and -0.77 (-1.40 to -0.14). Whereas rs4253778 was significantly associated with an increased level of ApoA I/ApoB100 ratio, Mean difference (95% CI) values was 0.80 (0.08 to 1.52). GMDR analysis showed a significant gene-gene interaction among rs4253778, rs1800206 of PPARα, rs9794, rs2016520 of PPARβ and rs10865710, rs3856806, rs709158, rs1805192 of PPARγ for eight-dimension models (P = 0.01), in which prediction accuracy was 0.624 and cross-validation consistency was 7/10.</p><p><b>CONCLUSIONS</b>The rs1800206 of PPARα and rs3856806 of PPARγ are significantly associated with a decreased level of ApoA I/ApoB100 ratio while rs4253778 of PPARα is associated with an increased level of ApoA I/ApoB100 ratio. There is a gene-gene interaction between multiple SNPs.</p>

ApoB gene genetic polymorphism of Han nationality and Mongolian nationality in midwest area of Inner Mongolia / 法医学杂志

OBJECTIVE@#To study ApoB gene genetic polymorphism of Han nationality and Mongolian nationality in midwest area of Inner Mongolia.@*METHODS@#Some unrelated individuals of Han nationality and Mongolian nationality in midwest area of Inner Mongolia were selected. Polymerase chain reaction-restriction fragment length polymorphism technology was used to check the presence of Xba I (X+) and EcoR I (E-) sites of rare alleles. The genotype frequency, allelic frequency and population genetics parameters were calculated.@*RESULTS@#The frequencies of Xba I (X+) and EcoR I (E-) rare alleles were 2% and 4.6% in Han population. There was no Xba I (X+) or EcoR I (E-) rare alleles found in Mongolian nationality.@*CONCLUSION@#The allelic frequencies of ApoB gene Xba I and EcoR I sites are very different in different races. These sites may be used in identification of ethnicity.

Studies of influences of blood glucose controlling on the changes of lipid profiles, ApoB100, ApoAI and HDL subclass of newly diagnosed type 2 diabetes / 生物医学工程学杂志

This study was aimed to observe if the lipid profiles, apoprotein B100 (ApoB100), ApoAI, high density lipoprotein (HDL) and its subclasses could be improved by controlling the blood glucose. Fifty-three patients with newly diagnosed type 2 diabetic were divided into four groups, diet and exercise group (n = 13), continuous subcutaneous insulin infusion (CSII) group (n = 14), multiple daily insulin injection group (MDI, n = 13), and oral hypoglycaemic agents group (n = 13). Fasting blood glucose (FPG), glycated hemoglobin A1c (HbA1c), lipid profiles, ApoB100, ApoAI and HDL subclasses were measured at beginning and a month later. Forty-three patients finished the testing. The levels of FPG, HbA1c, triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and ApoB100 were decreased significantly (P < 0.05) in all groups, and ApoAI/ApoB100 increased obviously (P < 0.05). Comparatively matured HDL subclasses such as HDL2b were increased (P < 0.05), and comparatively infantile HDL subclasses such as HDL3b were decreased (P < 0.05). Therapy with hyperglycemic agents improved TG, TC, LDL-C, ApoB100, ApoAI/ApoB100, and HDL2b significantly (P < 0.05), but intervention with the diet and exercise group alone did not improve lipid profiles, apolipoproteins, and HDL subclasses (P > 0.05). Meanwhile, therapy with insulin intensive therapy (MDI, CSII) group had the most powerful effect on decreasing ApoB100 concentration (P < 0.05). The results suggested that lipid profiles, apolipoproteins, and quantity and quality of HDL subclasses might be improved by blood glucose controlling.

genetic characterization of familial hypercholesterolemia in Pakistan

Familial hypercholesterolemia [FH] is caused by mutations in the genes coding for the low-density lipoprotein receptor [LDLR], apolipoprotein B-100, or proprotein convertase subtilisin/kexin type 9 [PCSK9]. In this study, a molecular analysis of LDLR gene and APOB gene was performed in a group of 17 unrelated patients from Pakistan. All patients were clinically diagnosed with definite or possible hypercholesterolemia according to a uniform protocol and internationally accepted WHO criteria. Mutational analysis included all exons, exon-intron boundaries and the promoter sequence of the LDLR, and fragments of exon 26 and exon 29 of APOB. In our study, SNPs within LDLR exon 12, rs688 and LDLR exon 13, rs5925 were identified. We identified associations between SNPs and increased levels of cholesterol in Pakistani population. We failed to detect polymorphisms in the APOB gene

Differential expressions of lipid metabolism related genes in the liver of young apoE knockout mice / 生理学报

The work was aimed to investigate the differential expressions of lipid metabolism related genes in the early stage of atherosclerosis in the young apolipoprotein E deficient (apoE(-/-)) mice at different ages with normal chow diet. The genotypes of mice were identified by using multiplex polymerase chain reaction (multi-PCR) analysis. The semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and real-time quantitative RT-PCR were used to analyze the expressions of lipid metabolism related genes in the liver of apoE(-/-) and age-matched wild type (WT) mice of 14-day old, 1-month old, 2-month old, 3-month old. The serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) contents were assayed using COD-PAP and GPO-PAP methods. The serum apolipoprotein B100 (apoB100) content was quantitated by immune turbidimetry. The hearts were perfusion-fixed in 4% formaldehyde, infiltrated with 30% gum sucrose for 24 h at 4 °C, and embedded in OCT compound. The aortic sinus tissues were serially sectioned at -15 °C, stained with Sudan IV, and counterstained with light green. The results were shown as follows. Compared with that in WT mice, the mRNA levels of apoA I and apoA IV in apoE(-/-) mice aged from 14-day old to 3-month old changed prominently (P<0.05), with apoA I up-regulated and apoA IV down-regulated. At the age of 1 month, the expression of apoB100 in apoE(-/-) mice was higher than that in WT mice (P<0.05). The expression of apoA V was up-regulated (P<0.05) and there was obvious lipid deposition in the aortic intima in apoE(-/-) mice at the age of 2 months. The expressions of fatty acid translocase (Fat/CD36) and angiopoietin-like protein 3 (Angptl 3) in apoE(-/-) mice were higher than those in WT mice at the age of 3 months (P<0.05), while the expressions of peroxisome proliferator-activated receptor α (PPARα), liver X receptor α (LXRα), carnitine palmitoyl transferase I (CPT I) and acyl coenzyme A oxidase 1 (ACOX1) showed no significant changes. The serum TC, TG, LDL-C and HDL-C contents in apoE(-/-) mice aged from 14-day old to 3-month old were higher than those in age-matched WT mice. apoE(-/-) mice showed a marked increase in serum apoB100 content, consistent with the trend of serum LDL-C content and apoB100 mRNA content in the liver. The results suggest that the mRNA expressions of apoA I, apoA IV, apoA V, apoB100 and Angptl 3 in apoE(-/-) mice change significantly compared with those in WT mice, and these genes might be relevant to the complicated lipid metabolism network, and involved in the early stage of atherogenesis.

Analysis of beta2-adrenergic receptor gene (beta2AR) Arg16Gly polymorphism in patients with endogenous hypertriglyceridemia in Chinese population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the Arg16Gly polymorphism of beta2-adrenergic receptor (beta2AR) gene and its association with endogenous hypertriglyceridemia (HTG) in Chinese population.</p><p><b>METHODS</b>Three hundred and forty one subjects including 100 HTG patients and 241 healthy controls from a population of Chinese Han nationality in Chengdu area were studied using polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLPs).</p><p><b>RESULTS</b>The frequencies of Gly allele at the Arg16Gly locus in combined group was 0.446, and were 0.427 and 0.490 in normal and HTG group, respectively. No significant difference was found in both allele and genotype frequencies between normal control and HTG group. The frequency of Gly allele at the Arg16Gly locus in beta2-adrenergic receptor gene in the population (0.446) was similar to that of Japanese (0.505), higher than that of American white(0.248), and lower than that of Polish population (0.633). In normal controls, subjects with genotype Arg/Arg had a higher concentration of serum TG and apoB100, and lower apoAII levels, when compared with those with genotypes Arg/Gly or Gly/Gly, respectively (vs. Arg/Gly for TG, vs. Gly/Gly for apoB100 and apoAII, respectively, P<0.05). In HTG group, subjects with genotype Arg/Arg had higher serum TC and low-density lipoprotein cholesterol levels when compared with those with Gly/Gly genotype (5.36+/-0.74 mmol/L vs. 4.77+/-1.07 mmol/L,P<0.05;3.03+/-0.70 mmol/L vs. 2.38+/-1.10 mmol/L,P<0.05).</p><p><b>CONCLUSION</b>These results suggest that the Arg16Gly polymorphism in beta2-adrenergic receptor gene are not only associated with serum TG,apoB100 and apoAII levels in the healthy Chinese subjects in Chengdu area, but also with serum TC and low-density lipoprotein cholesterol levels in subjects with endogenous hypertriglyceridemia. The Arg16Gly polymorphism in beta2-adrenergic receptor gene may be associated with TG and/or cholesterol metabolism in Chinese Han population.</p>

Mutation screening and functional analysis of low density lipoprotein receptor in a familial hypercholesterolemia family / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen the mutations of the low density lipoprotein receptor (LDLR) gene in a familial hypercholesterolemia (FH) family, and analyze the LDL-uptaking function of LDLR on lymphocytes of patients.</p><p><b>METHODS</b>Genomic DNA was extracted from four affected members in a Chinese FH family. The presence of apoB100 gene R3500Q mutation which results in familial defective apolipoprotein B100 (FDB) was excluded first. Fragments of the LDLR gene were amplified by touch-down polymerase chain reaction (Touch-down PCR) and analyzed by single-strand conformational polymorphism (SSCP). The suspect fragments of the LDLR gene were cloned and sequenced. Furthermore, the lymphocytes bounded with fluorescent-labeled LDL (DiI-LDL) were measured by fluorescence flow cytometry.</p><p><b>RESULTS</b>A nonsense mutation was identified in exon 10 of LDLR gene. This mutation gave rise to a premature stop codon (W462X), resulting in the absence of most of the LDLR domains. It was detected in all the affected members of the FH family. The ratios of functional LDLR in lymphocytes from patients and normal controls were 63.7% and 77.3% respectively. As a result, the activity of the functional LDLR in patients was just 82.4% of that in the normal controls.</p><p><b>CONCLUSION</b>It is possible that the W462X mutation of LDLR gene is the main cause for the disease in this family.</p>

Expression profiles of lipid metabolism-related genes in liver of apoE(-/-)/LDLR(-/-) mice / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the relationship between the expression characteristics of lipid metabolism-related genes in the liver and early atherosclerotic lesions in apolipoprotein E and low density lipoprotein receptor gene double knockout (apoE(-/-)/LDLR(-/-)) mice.</p><p><b>METHODS</b>RT-PCR was used to detect the differential expression of lipid metabolism-related genes in the liver of apoE(-/-)/LDLR(-/-) and wild type (WT) mice. Serum total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) level as well as aortic morphology were also analyzed.</p><p><b>RESULTS</b>Among the 11 lipid metabolism-related genes, apolipoprotein B100 (apoB100) mRNA levels were significantly higher in apoE(-/-)/LDLR(-/-)mice compared with WT mice. At 14 days, 1, 2 and 3 months of age, the level of mRNA expression were 1.55, 1.47, 1.50 and 2.42 folds of those of the age matched WT mice respectively. The fatty acid transporter (FAT/CD36) mRNA expression levels were higher in 14-day and 3-month old mice at 1.30 and 1.35 folds of those of the age matched WT mice, respectively. Apolipoprotein A IV (apoA IV) and Apolipoprotein AV (apoAV) mRNA levels were significantly down-regulated (0.89 fold decrease in 14-day, and 0.90 folds decrease in 3-month, respectively). The mRNA expression levels of apolipoprotein AI (apo AI), apolipoprotein F (apo F), peroxidase proliferator-activated receptor alpha (PPAR-alpha), liver X receptor alpha (LXRalpha), angiopoietin-like protein 3 (ANGPTL3), acyl-coenzymeA oxidase 1 (ACOX1) and carnitine palmitoyl transferase 1 (CPT1) had no significant changes. Serum TC, TG and LDL-C were higher than those of age matched WT mice at 7, 2 and 30 folds, respectively. Furthermore, apoE(-/-)/LDLR(-/-) mice demonstrated typical early atherosclerotic lesions at sinus and root regions of aorta in an age dependent manner.</p><p><b>CONCLUSION</b>Alterations of the expression of lipid metabolism-related genes in liver play important roles in the development of AS in the apoE(-/-)/LDLR(-/-) mice at early ages.</p>

Apolipoprotein B gene polymorphisms in people in the East Mediterranean area of Turkey

Point mutations in the receptor binding domain of low density lipoprotein may increase cholesterol levels in blood. Three mutations of Apo B-100 protein result in defective binding [Arg 3500 ----> [corrected] Gln, Arg 3500 ----> [corrected] Trp and Arg 3531 ----> [corrected] Cys]. We estimated the frequency of Apo B point mutations [codon 3500] C9774T [Arg 3500 ----> [corrected] Trp] and G9775A [Arg 3500 ----> [corrected] Gln] in 179 atherosclerotic, 145 hyperlipidaemic individuals and 272 healthy individuals in the east Mediterranean region of Turkey. Lipid and lipoprotein levels were measured with routine biochemical analyser and Apo B mutation was detected using real-time PCR. Neither mutation was found. In this region, Apo B-100 protein mutations are rare and causes of hyperlipidaemia and atherosclerosis may therefore be unrelated to them

Polymorphisms in the apolipoprotein B-100 gene: association with plasma lipid concentration and coronary artery disease.

BACKGROUND: The aim of this study was to investigate the association of apolipoprotein B gene polymorphisms with coronary artery disease and lipid levels in Indians. METHODS AND RESULTS: One hundred patients of angiographically proven atherosclerotic coronary artery disease and one hundred age- and sex-matched control subjects (treadmill negative) were included in the study. Serum lipids including cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, very low-density lipoprotein, and apolipoprotein B were analyzed. Genomic DNA was extracted and the apolipoprotein B 3' hypervariable region amplified by polymerase chain reaction. Regions carrying Xba1, EcoR1, and Msp1 restriction sites present in the apolipoprotein B gene were amplified and digested separately by the respective enzymes. Restriction fragment length polymorphism analysis showed that EcoR1 with the R+/R+ genotype was significantly more common in patients with coronary artery disease. Overall, the genotypes EcoR1+/+, Msp1+/+, Xba1+/+ and Eco R1+/+ Msp1+/-, Xba1-/- were significantly more common in patients as compared to controls (p<0.05). When gene polymorphisms were compared with lipid abnormalities, the genotypes EcoR1+/+, Xba1-/-, and Msp1+/+ were more frequent in patients with elevated apolipoprotein B and very low-density lipoprotein levels. On the other hand, these genotypes were less common in patients with increased total cholesterol and low-density lipoprotein levels. When we studied the individual alleles of the variable number of tandem repeats region, we observed that allele 34 was significantly increased in patients with coronary artery disease as compared to controls. Allele 36 was present with a frequency of 1% in controls while it was totally absent in patients. CONCLUSIONS: This study identifies the apolipoprotein B gene polymorphism associated with coronary artery disease. An association between apolipoprotein B gene polymorphisms and elevated apolipoprotein B and very low-density lipoprotein levels was observed. However, there was no positive association with other elevated lipid levels in North Indians from Uttar Pradesh.

The relationship of apolipoprotein H G1025C (Try316Ser) polymorphism with stroke and its effect on plasma lipid levels in Changsha Hans / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between G1025C (Try316Ser) polymorphism in exon 8 of apolipoprotein H (apoH) gene and stroke and to evaluate the effect of G1025C(Try316Ser) polymorphism on plasma lipid levels in Changsha Hans.</p><p><b>METHODS</b>G1025C (Try316Ser) polymorphism in apoH gene was determined by PCR-single strand conformation polymorphism analysis and DNA sequencing in 100 healthy controls, 260 patients with stroke, and 20 stroke pedigrees. Serum antiphospholipid antibody (APA) levels were tested by enzyme linked immunosorbent assay (ELISA). Plasma lipid levels were measured by routine methods.</p><p><b>RESULTS</b>No statistically significant differences were found in frequencies of genotypes and alleles of G1025C (Try316Ser) polymorphism between the controls and stroke patients. The serum levels of TG in the GC genotype of cerebral infarction patients and controls were markedly higher than those in GG genotype.</p><p><b>CONCLUSION</b>There was no association betweenG1025C (Try316Ser) polymorphism and stroke in Changsha Hans. G1025C (Try316Ser) polymorphism was associated with plasma lipid metabolism in Changsha Hans.</p>

Correlations among Serum Lipoprotein (a), LDL cholesterol, and Apolipoprotein (a) Concentrations in Liver Cirrhosis / 대한임상병리학회지

BACKGROUND: The structure of lipoprotein(a) [Lp(a)] includes a low-density lipoprotein cholesterol (LDL-C) component and apolipoprotein(a) [apo(a)] linked to apolipoprotein B-100 of LDL-C with a disulfide bond. Liver cirrhosis is the only disease in which the decrease of serum Lp(a) concentra-tion is observed as a secondary effect. In this study, we tried to investigate the mechanisms for the Lp(a) decrease in cirrhotic patients. METHODS: Forty Child 's class A cirrhotic patients, 40 Child 's class C patients from Asan Medical Center, and 80 healthy controls were recruited. Serum concentrations of interleukin-6 (IL-6), LDL-C, Lp(a), and free apo(a) were measured. RESULTS: The serum concentrations of Lp(a) in the Child 's class C patients were significantly lower than those in class A and the control group (P < 0.05). The apo(a) concentrations in the Child 's class C patients were significantly lower than those in class A and the control group (P < 0.05). The LDL-C concentrations of Child 's class C patients were significantly lower than those in class A and the con-trol group (P < 0.01). The IL-6 concentrations of Child 's class C patients were significantly higher than those in class A and the control group (P < 0.005). Serum concentrations of Lp(a) showed positive correlations with those of LDL-C (r=0.42, P < 0.0001) and with those of the free apo(a) (r=0.68, P < 0.0001). But serum concentrations of IL-6 had no correlation to those of the Lp(a) or the free apo(a). CONCLUSIONS: Considering the positive correlation between Lp(a) and LDL-C, the decrease in the serum Lp(a) in cirrhotic patients could be due mainly to the decrease in the LDL component, although we could not suggest the mechanism for the LDL decrease.

Apolipoprotein B-100/Apolipoprotein A-I Ratio is on Useful Indicator for Coronary Artery Disease in Koreans

BACKGROUND AND OBJECTIVES: Little is known about the relationship between the apolipoprotein (apo) B-100, or the apo B-100/apo A-I ratio, and coronary artery disease (CAD). The aim of this study was to investigate this association. SUBJECTS AND METHODS: Our study was carried out on 194 patients who had undergone elective coronary angiography (CAG), but had received no lipid-lowering medication. Patients with acute myocardial infarction were excluded. Stenosis of >or=50% in 1 or more coronary arteries was classified as CAD (+). RESULTS: HDL-C and apo A-I were significantly higher in females than in males (p=0.009 and 0.036). In our population we found that the apo A-I, HDL-C and the apo B-100/apo A-I ratio were significantly related to CAD (p=0.001, 0.006, and 0.007 respectively). In the male group (n=111), the apo B-100/apo A-I ratio was the only parameter statistically significant to CAD after correcting for age, diabetes mellitus and hypertension. Whereas, in the female group (n=83), the apo B/apo A-I ratio, apo B-100/apo A-I ratio, apo B-100, nonHDL-C, triglyceride, apo B, total cholesterol and low-density lipoprotein cholesterol were all significantly related to CAD (p=0.002, 0.003, 0.003, 0.007, 0.007, 0.009, 0.012 and 0.012 respectively). Of these parameters only the apo B-100/apo A-I ratio was significantly related to CAD in both female and male group. CONCLUSION: The apo B-100/apo A-I ratio is an useful indicator for discriminating between CAD (+) and CAD (-).

Changes of Plasma Lipoprotein(a) Levels as a Acute Phase Reactantfrom Antepartum to Postpartum Period / 대한산부인과학회잡지

Lipoprotein(a)[Lp(a)] represents a class of lipoprotein particles defined by the presence of apolipoprotein(a), a unique glycoprotein linked by a disulfide bond to apolipoprotein B-100 to form a single macromolecule. It was known that Lp(a) levels were associated with risk factor for cardiovascular disease and were fluctuated during pregnancy and postpartum. In the present study, plasma Lp(a) levels were estimated in two groups of women comprising 48 normal spontaneous vaginal delivery group and 52 Cesarean section delivery group. The changes of plasma Lp(a) concentrations were serially estimated before delivery, postpartum 1 weeks and postpartum 6 weeks. The result can be summarized as follows.1. Mean ploasma Lp(a) levels were changed from 43.9 +/- 28.4 mg/dl at delivery to 68.5 +/- 35.5 mg/dl at postpartum 1 weeks 73.1 +/- 35.7 mg/dl versus 63.7 +/- 35.1 mg/dl. And after postpartum 6 weeks, mean plasma Lp(a) levels were returned to near initial levels 48.4 +/- 21.1 mg/dl versus 42.2 +/- 16.7 mg/dl.3. Lp(a) levels were significantly rised postpartum 1 weeks compared with before delivery(p < 0.05) and after postpatum 6 weeks(p < 0.05). In conclusion, serum Lp(a) levels were increased postpartum 1 weeks with significant value, and returned to initial levels after postpartum 6 weeks. Our findings suggests that Lp(a) has the characteristics of an acute phase reactant rather modulated by endogenous hormone.