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Dorte?DamgaardEmail author Peter?H?Nissen Lillian?G?Jensen Gitte?G?Nielsen Anette?Stenderup Mogens?L?Larsen Ole?Faergeman 《BMC medical genetics》2005,6(1):15
Background
Familial Hypercholesterolemia (FH) is a common genetic disease and at the molecular level most often due to mutations in the LDL receptor gene. In genetically heterogeneous populations, major structural rearrangements account for about 5% of patients with LDL receptor gene mutations. 相似文献3.
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Very low density lipoproteins from guinea pig plasma, endogenously labeled with 3H in both the esterified and free cholesterol moieties, were obtained from serum collected 20 hr after the intravenous injection of 3H-cholesterol into donor animals. When these lipoproteins were injected into recipient guinea pigs, the esterified 3H-cholesterol was rapidly cleared from the plasma; 24% was in the liver in 5 min and 54% in 15 min. A smaller fraction of the esterified cholesterol appeared in other plasma lipoprotein fractions, with 3H in the low density lipoproteins reaching a peak of 9%-18% of the injected esterified 3H-cholesterol between 30 and 60 min after the injection. The results indicate that most of the esterified cholesterol in very low density lipoproteins of guinea pig plasma is removed directly by the liver and a minor fraction is transferred to low density lipoproteins. The pattern of labeling of cholesteryl esters of high density lipoproteins in these experiments suggests that their low concentration in the guinea pig is accompanied by a rapid turnover rate. 相似文献
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The concentration of lipids, lipoproteins and apolipoprotein A-I and B was measured in the plasma of 33 patients, enrolled in a double-blind, controlled trial of alprenolol in myocardial infarction, after one year on the study medication and again after 6 months off the medication. Sixteen patients received 200 mg alprenolol twice daily and 17 received placebo. There were no statistically significant differences between the parameters in the two groups after one year on medication. However, when medication was stopped, the ratio of apolipoprotein B to apolipoprotein A-I fell by 9% in the alprenolol group and increased by 2% in the placebo group. This difference was statistically significant. Our results suggest that alprenolol, a beta-blocker with weak intrinsic sympathomimetic effect, has slight effects on plasma lipoproteins. These effects were apparent only by measurements of apolipoproteins. 相似文献
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H K Jensen L G Jensen H Meinertz P S Hansen N Gregersen O Faergeman 《Atherosclerosis》1999,146(2):337-344
Heterozygous familial hypercholesterolemia (FH) is one of the most common potentially fatal single-gene diseases leading to premature coronary artery disease, but the majority of heterozygous FH patients have not been diagnosed. FH is due to mutations in the gene coding for the low-density lipoprotein (LDL) receptor, and molecular genetic diagnosis may facilitate identification of more FH subjects. The Danish spectrum of 29 different mutations, five of which account for almost half of heterozygous FH, is intermediate between that of countries such as South Africa, where three mutations cause 95% of heterozygous FH in the Afrikaners, and Germany or England, where there are many more mutations. In clinical practice, a strategy for the genetic diagnosis of heterozygous FH, tailored to the mutational spectrum of patients likely to be seen at the particular hospital/region of the country, will be more efficient than screening of the whole LDL receptor gene by techniques such as single-strand conformation polymorphism (SSCP) analysis in every heterozygous FH candidate. In Aarhus, Denmark, we have chosen to examine all heterozygous FH candidates for the five most common LDL receptor gene mutations (W23X, W66G, W556S, 313 + 1G --> A, 1846 - 1G --> A) and the apoB-3500 mutation by rapid restriction fragment analysis. Negative samples are examined for other mutations by SSCP analysis followed by DNA sequencing of the exon indicated by SSCP to contain a mutation. If no point mutation or small insertion/deletion is detected, Southern blot or Long PCR analysis is performed to look for the presence of large gene rearrangements. In conclusion, our data suggest that an efficient molecular diagnostic strategy depends on the composition of common and rare mutations in a population. 相似文献
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O Faergeman 《European heart journal》2001,22(7):526-528
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Rat very low density lipoproteins (d smaller than 1.006), biologically labeled in esterified and free cholesterol, were obtained form serum 6 h after intravenous injection of particulate (3-H) cholesterol. When injected into recipient animals, the esterified cholesterol was cleared form plasma with a half-life of 5 min. After 15 min, 71% of the injected esterified (3-H) cholesterol had been taken up by the liver, where it was rapidly hydrolyzed. After 60 min only 3.3% of the amount injected had been transferred, via lipoproteins of intermediate density, to the low density lipoproteins of plasma (d 1.019-1.063). Both uptake in the liver and transfer to low density lipoproteins occurred without change of distribution of 3-H in the various cholesteryl esters. 3-H appearing in esterified cholesterol of high density lipoproteins (d greater than 1.063) was derived from esterification, presumably by lecithin: cholesterol acyltransferase, of simultaneously injected free (3-H) cholesterol. Content of free (3-H) cholesterol in the very low density lipoproteins used for injection could be reduced substantially by incubation with erythrocytes. This procedure, however, increased the rate of clearance of the lipoproteins after injection into recipient rats. These studies show that hepatic removal is the major catabolic pathway for cholesteryl esters of rat very low density lipoproteins and that transfer to low density lipoproteins occurs to only a minor extent. 相似文献
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