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91.
Predominance of a 6 bp deletion in exon 2 of the LDL receptor gene in Africans with familial hypercholesterolaemia
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Thiart R Scholtz CL Vergotine J Hoogendijk CF de Villiers JN Nissen H Brusgaard K Gaffney D Hoffs MS Vermaak WJ Kotze MJ 《Journal of medical genetics》2000,37(7):514-519
In South Africa, the high prevalence of familial hypercholesterolaemia (FH) among Afrikaners, Jews, and Indians as a result of founder genes is in striking contrast to its reported virtual absence in the black population in general. In this study, the molecular basis of primary hypercholesterolaemia was studied in 16 Africans diagnosed with FH. DNA analysis using three screening methods resulted in the identification of seven different mutations in the coding region of the low density lipoprotein (LDLR) gene in 10 of the patients analysed. These included a 6 bp deletion (GCGATG) accounting for 28% of defective alleles, and six point mutations (D151H, R232W, R385Q, E387K, P678L, and R793Q) detected in single families. The Sotho patient with missense mutation R232W was also heterozygous for a de novo splicing defect 313+1G→A. Several silent mutations/polymorphisms were detected in the LDLR and apolipoprotein B genes, including a base change (g→t) at nucleotide position −175 in the FP2 LDLR regulatory element. This promoter variant was detected at a significantly higher (p<0.05) frequency in FH patients compared to controls and occurred in cis with mutation E387K in one family. Analysis of four intragenic LDLR gene polymorphisms showed that the same chromosomal background was identified at this locus in the four FH patients with the 6 bp deletion. Detection of the 6 bp deletion in Xhosa, Pedi, and Tswana FH patients suggests that it is an ancient mutation predating tribal separation approximately 3000 years ago.
Keywords: apolipoprotein B; hypercholesterolaemia; low density lipoprotein receptor; mutation 相似文献
Keywords: apolipoprotein B; hypercholesterolaemia; low density lipoprotein receptor; mutation 相似文献
92.
目的:观察血凝素氧化低密度脂蛋白受体-1(LOX-1)对氧化LDL(ox-LDL)诱导的人脐静脉内皮细胞(human unbilical vein endothelial cells, HUVECs)表达单核细胞趋化蛋白(monocyte chemoattractant protein-1, MCP-1)基因及蛋白的影响。 方法: 用RT-PCR和Western blot的方法观察ox-LDL对培养的HUVECs表达LOX-1和MCP-1基因及蛋白的影响,然后用LOX-1的受体阻滞剂爱兰苔胶(carrageenan) 和聚肌苷酸[polyinosinic acid,poly(I)]与HUVECs预先作用后,再观察内皮细胞表达LOX-1和MCP-1基因和蛋白的变化。 结果: 用不同浓度的ox-LDL(0 mg/L、10 mg/L、20 mg/L 、50 mg/L、100 mg/L)与HUVECs培养24 h后,LOX-1和MCP-1的mRNA和蛋白的表达明显增加,呈浓度依赖性;用Carrageenan 和polyinosinic acid与HUVECs预先作用2 h后,再加入50 mg/L的ox-LDL培养24 h,与未加Carrageenan和polyinosinic acid相比,HUVECsLOX-1和MCP-1的mRNA和蛋白的表达明显减少。 结论: ox-LDL可以调节培养的HUVECsLOX-1和MCP-1基因和蛋白的表达,LOX-1作为ox-LDL的特异性受体,可能介导了ox-LDL诱导血管内皮细胞分泌MCP-1,从而在动脉粥样硬化的发生发展中起着重要的作用。 相似文献
93.
Lectin-like oxidized low density lipoprotein receptor-1 (LOX-1 } is a type-Ⅱ membrane protein belonging to the C-type lectin family molecules, which acts as a cell surface endocytosis receptor for atherogenic oxidized LDL (Ox-LDL). LOX-1 supports the binding internalization and proteolytic degradation of oxidized LDL, but not of significant amounts of acetylated LDL. LOX-1 is initially synthesized as a 40 kD precursor protein with N-linked high mannose-type carbohydrate, which is further glycosylated and processed into a 48-kD mature form. In vivo, endothelial cells that cover early therosclerotic lesions, intimal macrophages and smooth muscle cells in advanced atherosclerotic plaques express LOX-1. LOX-1 is cleaved at membrane proximal extracellular domain and released from the cell surface. Measurement of soluble LOX-1 in vivo may provide novel diagnostic strategy for the evaluation and prediction of atherosclerosis and vascular diseases. 相似文献
94.
Antioxidant enzymes and paraoxonase show a co-activity in preserving low-density lipoprotein from oxidation 总被引:1,自引:0,他引:1
Sözmen EY Sözmen B Girgin FK Delen Y Azarsiz E Erdener D Ersöz B 《Clinical and experimental medicine》2001,1(4):195-199
Oxidative modification of low-density lipoprotein in the artery wall plays a crucial role in the development of atherosclerosis.
This physiopathological mechanism is clearly inhibited by high-density lipoprotein possibly via paraoxonase enzyme activity,
present in high-density lipoprotein. In this study we determined the in vitro susceptibility of low-density lipoprotein to
oxidation and the effect of various factors, such as paraoxonase phenotypes, on this process. Low-density lipoprotein from
healthy volunteers (n=66) was isolated using the precipitant reagent and the oxidation was evaluated by measuring the malonyl dialdehyde and diene
levels. Low-density lipoprotein cholesterol and phospholipid, vitamin E, serum cholesterol, high-density lipoprotein and low-density
lipoprotein cholesterol levels, and erythrocyte antioxidant enzymes were also determined. There was no difference among the
parameters with regard to gender. Low-density lipoprotein samples obtained from subjects with the AA allele were more prone
to oxidation, as observed by their higher stimulated conjugated diene (P=0.041) and thiobarbituric acid-related substance (P=0.042) levels, than samples from subjects with AB or BB alleles. The subjects with the BB allele had higher superoxide dismutase
(P=0.021) and catalase (insignificant increase) activities, while their conjugated diene (P=0.000) levels were lower. In conclusion, our results revealed that the high low-density lipoprotein oxidation is related
to the high low-density lipoprotein cholesterol content and low phospholipid content. The present study demonstrated an increase
in superoxide dismutase and catalase activities, asl well as PON1 activities, in subjects with the BB allele. Since these
enzymes all show activity against low-density lipoprotein oxidation, we propose that future investigations on atherosclerotic
processes should address PON1 polymorphism as well as PON1 and other antioxidant enzymes.
Received: 7 May 2001 / Accepted: 14 December 2001 相似文献
95.
A. A. Nikiforova A. A. Kuz'min W. Richter 《Bulletin of experimental biology and medicine》1995,120(3):962-964
In vitro experiments show that sodium citrate in a final concentration of 130 mM induces a 4- to 5-fold increase in the activity of
lecithin-cholesterol acyltransferase. A parallel determination of the blood content of primary products of lipid peroxidation
reveals a 20–30% decrease in diene and triene conjugates and lipid hydroperoxides.
Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 120, N
o
9, pp. 323–325, September, 1995
Presented by A. N. Klimov, Member of the Russian Academy of Medical Sciences 相似文献
96.
One hundred and sixty-three healthy Chinese subjects of both sexes were studied for serum paraoxonase (PON) polymorphism, and levels of lipids and apolipoproteins in order to examine effects of PON alleles on these parameters. The level of serum triglyceride was significantly higher in high activity allele (PON*B) compared with that in low activity allele (PON*A) in both sexes (P less than 0.01). The subjects with PON A had significantly higher LDL cholesterol (P less than 0.05) and lower Apo A-II and ApoB levels. The influence of serum paraoxonase on serum lipids was estimated further by Spearman's rank correlation. In the males, there was a significant negative correlation of serum paraoxonase activity with total (P less than 0.05) and LDL (P less than 0.01) cholesterol levels, and positive correlation with HDL cholesterol and Apo A-II levels (P less than 0.05). Serum paraoxonase activity had a high positive correlation with serum triglyceride levels in both sexes (P less than 0.001). Serum ApoB level had a positive correlation with the enzyme activity only in females (P less than 0.01). The allelic effect of PON on these parameters was studied by multiple regression analysis. The high activity allele (PON*B) was associated with higher serum triglyceride level (P less than 0.001) and ApoB (P less than 0.001), while it had lowering influence on total cholesterol (P less than 0.05) and LDL cholesterol (P less than 0.005) in men. The average allelic effect of PON was found to be about 22% for serum triglycerides, 11% for LDL cholesterol, 14% for Apo A-II and 19% for Apo B in the present study. This study suggests a possible significant role of serum paraoxonase alleles in the metabolism of serum lipids and apolipoproteins. 相似文献
97.
制备了硫酸酯化魔芋葡甘聚糖凝胶颗粒血液低密度脂蛋白吸附剂,扫描电镜观察产物呈交联网状多孔结构。体外静态吸附实验表明:在37℃振荡吸附2h后,对总胆固醇(TC)、低密度脂蛋白及超低密度脂蛋白胆固醇(LDL+VLDL-C)、高密度脂蛋白胆固醇(HDL-C)的吸附率分别为52.68%、54.76%、27.78%。通过吸附动力学曲线和吸附等温线分析,吸附剂对LDL+VLDL-C的作用包括类似分子筛的吸附和电荷间静电相互作用两种方式。 相似文献
98.
Bernice R. Zysow Clive R. Pullinger Lori K. Hennessy Robert V. Farese Jr. Marjan Ghassemzadeh John P. Kane 《Clinical genetics》1994,45(6):292-297
The rare apolipoprotein C-II (apoC-II) mutation, apoC-IILys19→Thr , also known as apoC-II-v, has been found previously in association with hyperlipoproteinemia. From a lipid clinic screening we identified three unrelated individuals who had the apoC-IILys19→Thr mutation. Among eight family members of one proband, we have found another four who were affected. None of the inviduals in this kindred is dyslipidemic and there is no difference in lipid levels between affected and unaffected family members. Therefore, we conclude that the presence of this apolipoprotein variant by itself has no effect on lipoprotein levels. In addition, the apolipoprotein E (apoE) isoform, apoE4 does not have a synergistic effect on lipoprotein levels in this kindred, in contrast to observations on the interaction of apoE4 with another apoC-II mutant (apoC-IIToronto ). The single nucleotide substitution that causes the apoC-IILys19→Thr variant introduces a previously unrecognized restriction site (for Mae III), that provides for easy screening. 相似文献
99.
T. N. Ivanova E. D. Polyakova A. M. Olfer'ev N. V. Perova 《Bulletin of experimental biology and medicine》1998,125(5):505-508
The rate of cholesterol synthesis in peripheral blood lymphocytes and plasma lipid and lipoprotein spectra are studied in
patients with isolated hypercholesterolemia and combined hyperlipidemias (IIa and IIb hyperlipidemias according to Frederickson
classification).14C-acetate incorporation into cholesterol in peripheral blood lymphocytes is considerably higher in patients with type IIb
hyperlipidemia. Lipanthyl-200M reduces the rate of cholesterol synthesis in lymphocytes of both groups. A direct correlation
is established between serum triglyceride level and the rate of cholesterol synthesis.
Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 125, No. 5, pp. 569–573, May, 1998 相似文献
100.
H Zhuang A G Coulepis S A Locarnini J Kaldor J A Marshall I D Gust 《Journal of medical virology》1983,11(4):267-276
During a search for the aetiological agent of non-A non-B hepatitis, a precipitating antigen was detected in the sera of some patients during the acute phase of their illness. The antigen was detected by agar gel diffusion using antibody from convalescent sera obtained from patients with non-A non-B hepatitis, and from haemophiliac sera. The antigen was usually detected early in the patient's illness, disappearing as liver function tests returned to normal. In some patients specific antibody appeared during the convalescent phase of the disease. The antigen does not appear to be specific for non-A non-B hepatitis, as it could be detected with similar frequency in patients with hepatitis A or hepatitis B and some patients with other liver disorders. Biochemical and biophysical studies suggest that the antigen is probably an abnormal lipoprotein produced as a result of acute liver damage. 相似文献