Eight novel LDL receptor gene mutations among patients under LDL apheresis in Dresden and Leipzig.

LDL apheresis is highly efficient in reducing elevated plasma cholesterol. Due to strict indications only patients with severe, refractory hypercholesterolemia are treated with this method. Mutations in the LDL receptor gene are major genetic causes for severe hypercholesterolemia. Screening the entire gene in LDL apheresis patients from Saxony should determine whether an increased frequency of defined mutations is responsible for the atherogenic hypercholesterolemia in this group. 31 unrelated patients (15 male, 16 female, age 33-71 yrs.) were included in the analysis. The LDL-R gene was screened using SSCP and/or automated sequencing. The familial defective apolipoprotein B-100 (FDB) mutation was genotyped using established PCR techniques. Nineteen of 31 patients were carriers of an LDL-R mutation. Ten missense and two nonsense mutations, three insertions and two deletions were detected. The mutations C74S, C74R, T87M, 660delC, 662insCCCCG, 680insGGACAAATCTGA, 1428insC and 2167delG have not been previously described. One patient was compound heterozygous for two missense mutations. Two further patients were heterozygous for FDB. No mutations were found among controls. A genetic background for hypercholesterolemia in the LDL-R could be established in about 61% of the patients examined. Therefore, methods of DNA analysis allow to recognize and adequately treat a large portion of high-risk individuals at an early stage.

[Vitamin E distribution of lipoproteins in patients with coronary heart disease]. / Vitamin-E-Verteilung der Lipoproteine bei Patienten mit koronarer Herzerkrankung.

The oxidative modification of LDL could play an important role for the development of atherosclerosis. The present study was undertaken to compare the concentration of vitamin E in serum and lipoproteins between patients with coronary heart disease and a healthy control group. The study included 36 male patients with angiographically established coronary three-vessel disease and 32 healthy volunteers. Cholesterin, triglyceride, LDL-cholesterin, HDL-cholesterin, and vitamin E in serum and in lipoproteins were determined. The serum vitamin E concentration in the patients group was significantly higher than in controls. However, vitamin E was correlated with cholesterin in both groups. The distribution of vitamin E in healthy volunteers was LDL 53%, HDL 34% and VLDL 13%, whereas that in patients was LDL 57%, HDL 26% and VLDL 16%. The level of vitamin E in LDL was in the patient group significantly higher and correlated with the vitamin E- and the cholesterin-concentration in serum. The ratio vitamin E/cholesterin in LDL was in patients discretely lower, whereas the same ratio in HDL was higher. The results suggest that also in patients with coronary artery disease vitamin E is related to the lipid concentration. The decreased ratio vitamin E/cholesterin in LDL could be attributed to the oxidative modification of LDL.

[HDL subfractions in post-prandial lipidemia]. / HDL-Subfraktionen unter postprandialer Lipämie.

The influence of a standardised fatty test meal on the composition of high-density lipoprotein (HDL) subfractions (HDL3, HDL2) and the concentration of other lipid parameters was investigated in a group of young women of the age 20-25 years, in women of the age range 60-90 years, and in a group of patients with arteriosclerotic diseases. Total cholesterol and HDL cholesterol in serum do not change significantly under extreme conditions of postprandial lipaemia. This is true also regarding persons in high age groups and patients with arteriosclerotic diseases. In contrast to the group of young subjects, 60-90 years old women show both elevated HDL triglyceride levels under basal conditions and a greater magnitude of HDL triglyceride enrichment under the conditions of postprandial lipaemia. Patients with arteriosclerotic diseases also exhibit a marked postprandial HDL triglyceride enrichment. It is concluded that there are metabolic relations between the observed low HDL2 cholesterol concentrations in the group of older subjects and in patients with arteriosclerotic diseases and the high magnitude of HDL triglyceride increase in the postprandial state which are relevant within the risk syndrome hypertriglyceridaemia-low HDL2 levels.

[Oral fat tolerance test in obese patients]. / Oraler Fettbelastungstest bei Adipösen.

19 adipose patients, 10 of them women, underwent an oral fat tolerance test with circa 50 g triglycerides. Before the loading test as well as 2 and 4 hours after it the serum lipids were determined. While in the cholesterol components (including the index of arteriosclerosis) no significant shiftings were the result, after 2 hours in the triglycerides a significant increase (p less than 0.05) by 21% from 1.62 +/- 0.76 to 1.96 +/- 0.91 mmol/l could be stated. The further increase after 4 hours by 10% was not significant. A standardized fat tolerance test concerning the triglycerides is apparently better suited for the estimation of the atherogenic risk than the determination of the fasting value alone.-By an additional determination of LPL and insulin as key enzyme and hormone, respectively, probably better statements could be made, which under equal conditions explain the interindividual differences of adipose persons in weight gain and weight reduction.

[Subfractions of high density lipoproteins in relation to age]. / Subfraktionen der High-density-Lipoproteine (HDL) in Abhängigkeit vom Lebensalter.

In dependence on age women show both elevated levels of serum triglycerides and changes of lipid composition of HDL. A decrease of HDL- and HDL2-cholesterol levels and an increase of HDL- and HDL2-triglyceride concentrations are seen in the group of older persons. The concentration of HDL3-phospholipids decreases in dependence on aging. The content of triglycerides and the relation triglyceride/cholesterol of the subfraction HDL2, but not of HDL3, show positive correlations with the level of serum triglycerides. These changes are related to an age-dependent decrease of post-heparin lipolytic activity and a remodulation of HDL in dependence on the relation of the concentration of triglyceride rich lipoproteins and HDL.