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G Assmann

Publications and source records attributed to G Assmann.

At least 19 recordsLinked to original sources
PubMed1992

Role of triglycerides in coronary artery disease: lessons from the Prospective Cardiovascular Münster Study.

The incidence of atherosclerotic coronary artery disease (CAD) was assessed in 4,576 male participants of the Prospective Cardiovascular Münster (PROCAM) study, aged 40-64 years, over a 4-year follow-up period. In this time, 122 study participants developed atherosclerotic CAD (89 definite nonfatal myocardial infarctions and 33 definite atherosclerotic CAD deaths). Univariate analysis revealed a significant association between the incidence of atherosclerotic CAD, and high-density lipoprotein (HDL) cholesterol (p < 0.001) and triglyceride (p < 0.01) levels. The relation to HDL cholesterol remained after adjustment for other risk factors. By contrast, the relation between the incidence of atherosclerotic CAD and triglycerides disappeared if, in a multivariate analysis by means of a multiple logistic function, cholesterol or HDL cholesterol was taken into account. However, the data suggested that hypertriglyceridemia is a powerful additional coronary risk factor, when excessive triglycerides coincide with a high ratio (> 5.0) of plasma low-density lipoprotein (LDL) cholesterol to HDL cholesterol. Even though the prevalence of this subgroup was only 3.7%, it included a quarter of all atherosclerotic CAD events observed.

Adolescent↗
PubMed1992

Relation of high-density lipoprotein cholesterol and triglycerides to incidence of atherosclerotic coronary artery disease (the PROCAM experience). Prospective Cardiovascular Münster study.

The incidence of atherosclerotic coronary artery disease (CAD) was assessed in 4,559 male participants (aged 40 to 64 years) from the Prospective Cardiovascular Münster study, over a 6-year follow-up period. During this time, 186 study participants developed atherosclerotic CAD (134 definite nonfatal myocardial infarctions and 52 definite atherosclerotic CAD deaths including 21 sudden cardiac deaths and 31 fatal myocardial infarctions). Univariate analysis revealed a significant association between the incidence of atherosclerotic CAD and high-density lipoprotein (HDL) cholesterol (p less than 0.001) and triglycerides (p less than 0.001). The relation to HDL cholesterol remained after adjustment for other risk factors. By contrast, the relation between the incidence of atherosclerotic CAD and triglycerides disappeared if, in a multivariate analysis by means of a multiple logistic function, cholesterol or HDL cholesterol were taken into account. However, the data suggested that hypertriglyceridemia is a powerful additional coronary risk factor, when excessive triglycerides coincide with a high ratio of plasma low-density lipoprotein cholesterol to HDL cholesterol (greater than 5.0). Even though the prevalence of this subgroup was only 4.3%, it included a quarter of all atherosclerotic CAD events observed.

Adult↗
PubMed1992

The importance of triglycerides: results from the Prospective Cardiovascular Münster (PROCAM) Study.

In the PROCAM study hypertriglyceridaemia was much more common among men (18.6%) than women (4.2%). Prevalence increased with age in women, but remained nearly constant at about 20% in men aged 35 years or more. In a multiple regression analysis a strong negative correlation between triglycerides and HDL cholesterol was found. A positive relationship was observed with cholesterol, blood glucose, factor VIIc, and PAI-1 in both sexes. Only in men, triglycerides are positively correlated with Apo A-I, body mass index, cigarette smoking, and alcohol consumption. Postmenopausal women showed higher triglyceride levels than premenopausal women. No independent relationships were observed to age, blood pressure, Lp(a), Apo A-II, Apo B, AT-III, protein C, fibrinogen, and oral contraceptives. A longitudinal analysis of data from 4474 male PROCAM participants aged 40-64 years with a follow-up of 4 years did not identify triglycerides as an independent risk factor, but the data suggest hypertriglyceridaemia is an additional risk factor for CHD, when excessive triglycerides coincide with a high ratio of plasma cholesterol to HDL-cholesterol and with low HDL-cholesterol values.

Adolescent↗
PubMed1992

Comparative effects of a recommended lipid-lowering diet vs a diet rich in monounsaturated fatty acids on serum lipid profiles in healthy young adults.

This crossover study investigated the effects of two fat-reduced diets, one rich in monounsaturated fatty acids (MUFAs), the other rich in polyunsaturated fatty acids (PUFAs), on serum lipid profiles in 38 healthy young adults initially on a typical western diet. After being randomly assigned to two groups, the subjects received the MUFA or PUFA diet for 3-wk and then the other diet for 3 wk. Both test diets led to significant reductions in serum cholesterol, LDL cholesterol, and HDL cholesterol (P less than 0.001). Both reduced apolipoprotein B (P less than 0.001) and apolipoprotein A-I concentrations (P less than 0.01 for the MUFA, P less than 0.001 for the PUFA diet). Apolipoprotein A-I was significantly higher on the MUFA than on the PUFA diet. The ratio of apolipoprotein A-I to B significantly increased on both diets. Thus, a low-fat, MUFA-rich diet is as effective as a low-fat, PUFA-rich diet in lowering total and LDL cholesterol, but both also lowered HDL cholesterol concentrations. The MUFA-rich diet may be more advantageous than the PUFA-rich one because it does not lower apolipoprotein A-I concentrations as much as the PUFA-rich diet.

Adult↗
PubMed1992

Severe type III hyperlipoproteinemia associated with unusual apolipoprotein E1 phenotype and epsilon 1/'null' genotype.

A 60-year-old white male (KH) was diagnosed to suffer from severe type III hyperlipoproteinemia (HLP) and premature cardiovascular disease. Biochemical analysis revealed an unusual apolipoprotein (apo) E phenotype and genotype. All clinical characteristics of type III HLP were present in the patient. His very low density lipoprotein (VLDL) cholesterol to plasma triglyceride (TG) ratio was elevated at 0.97 without therapy which is unusually high (normal ratio about 0.18). By contrast his plasma apo E level was only moderately elevated (6.8 mg dl-1). The patient's apo E migrated in the apo E1 position on isoelectric focusing gels. Chemical modification with cysteamine and treatment with neuraminidase confirmed the presence of two cysteine residues in the patient's apo E and a normal sialylation pattern. Pedigree analysis suggested that the patient was a compound heterozygote with one apo epsilon 1 allele and another allele whose product did not appear in the plasma compartment ('null' allele). Direct sequencing of polymerase chain reaction (PCR) amplified segments of the apo E gene as well as restriction fragment length polymorphism (RFLP) analysis with the endonuclease Taq I identified an adenosine for guanosine (G-->A) exchange in the second base of codon 127 that is predictive for an Asp for Gly substitution in the encoded apo E amino acid sequence. This mutation is the structural basis for the apo E1 isoform identified upon isoelectric focusing. Five other family members are also carriers of the mutant apo epsilon 1 allele. Two of those were hyperlipidemic and exhibited biochemical characteristics of type III HLP. A second mutation, a deletion of a G in codon 31, is predictive for a reading frameshift that encodes for a premature stop in codon 60. Our inability to identify the product of a second apo E allele in the plasma of the patient and two other members of the KH family corresponds with the heterozygous presence of this mutation in the affected individuals. Both relatives (like the index case) had an increased VLDL cholesterol to plasma TG ratio, which indicates the presence of cholesterol-enriched VLDL particles. We propose that the single base deletion in the apo E gene which is the cause of a non-functional 'null' allele in addition to a probably dominant apo E1 (Gly127-->Asp, Arg158-->Cys) variant of late or incomplete penetrance are the primary genetic defects in this kindred leading to severe dysbetalipoproteinemia.

Adolescent↗
PubMed1992

Determination of apolipoprotein B in apolipoprotein CII/CIII-containing lipoproteins by an immunoenzymmetric assay.

A solid phase sandwich immunoenzymmetric assay is described for the determination of apolipoprotein B in apolipoprotein CII- and/or CIII-containing lipoproteins (chylomicron remnants, VLDL, IDL). During a first incubation step the particles containing apolipoproteins CII and/or CIII are bound to antibodies against these components, while the antibodies are immobilised on microtitre plate wells. After washing, anti-apolipoprotein B is added in a second incubation step. Finally peroxidase-labelled anti-sheep IgG reacts with the bound anti-apolipoprotein B, thus allowing the quantification of complexes containing both B and CII/CIII apolipoproteins. The amounts of these complexes were correlated with total cholesterol, triacylglycerols, HDL- and LDL-cholesterol, apolipoproteins AI and B, as well as with age and sex of the subject. A total of 258 individuals was studied, including patients with lipid metabolism disorders, patients with manifest coronary heart disease, and healthy controls. The assay described in this article was compared with radial immunodiffusion after pretreatment of samples. The immunoenzymmetric assay was easier and faster to perform and had a lower detection limit than the classical VLDL apolipoprotein B determination using ultracentrifugation. Furthermore, it could be performed directly on native serum. Most importantly, the study revealed elevated apolipoprotein CII/CIII-B levels in coronary heart disease patients of both sexes compared with normal subjects. Furthermore, in male coronary heart disease patients a negative correlation was found between the concentrations of apolipoprotein CII/CIII-B and HDL-cholesterol. These results suggest a delayed VLDL-HDL exchange of lipids and proteins in these patients which results in an accumulation of atherogenic apolipoprotein B-containing VLDL and IDL.

Adult↗
PubMed1992

Nonsynonymous polymorphic sites in the apolipoprotein (apo) A-IV gene are associated with changes in the concentration of apo B- and apo A-I-containing lipoproteins in a normal population.

The aims of this study were to detect polymorphic sites in the apolipoprotein (apo) A-IV gene, to establish their frequencies, to determine potential haplotypes, and to investigate the role of these polymorphisms in lipid metabolism. A sequencing study of four individuals led to the identification of two synonymous mutations (codons 9 and 54) and three nonsynonymous mutations (Val-8----Met, Gln360----His, and Thr347----Ser) and of a VNTR polymorphism within a series of three or four CTGT repeats in the noncoding region of exon 3. Frequencies of these polymorphisms were determined in 291 students by using naturally occurring (BstEII for the synonymous mutation in codon 54, HinfI for Thr347----Ser, and Fnu4HI for Gln360----His) or artificially introduced restriction-enzyme cutting sites (BstEII for the synonymous mutation in codon 9 and MamI for Val-8----Met), subsequent to PCR amplification. The four-base deletion/insertion polymorphism and its localization cis or trans to the mutations in codons 347 and 360 were studied by direct sequencing of PCR-amplified DNA from 87 students. Frequencies of the rarer alleles were .007 for apo A-IV-8:Met, .04 for the synonymous mutation in codon 9, .14 for the synonymous mutation in codon 54, .16 for apo A-IV347:Ser, .07 for apo A-IV360:His, and .39 for the four-base of insertion. Apo A-IV360:His in all cases was cis-localized to the (CTGT)3 repeat and apo A-IV347:Thr; and apo A-IV347:Ser was cis-localized to the (CTGT)4 repeat and apo A-IV360:Gln. Four haplotypes formed from these three polymorphic sites were thus found. The apo A-IV347:Ser allele was associated both with significantly lower plasma apo B concentrations in both sexes and with significantly lower LDL-cholesterol concentrations in men. Heterozygous carriers of apo A-IV360:His exhibited significantly higher concentrations of LDL-cholesterol and lower Lp(a) concentrations, compared with apo A-IV360:Gln homozygotes. We could not confirm the previously reported association of apo A-IV360:His with elevated HDL-cholesterol concentrations. In the population, the Val-8----Met polymorphism was not associated with significantly different lipid concentrations, but in a family study the Met-8 allele was associated with lower HDL-cholesterol and higher LDL-cholesterol concentrations. In conclusion, our results indicate an important role of the apo A-IV gene locus in the metabolism of apo B and, to a lesser extent, apo A-I containing lipoproteins.

Adult↗
PubMed1992

[Relationship between lipid metabolism disorders and age of first manifestations of coronary heart disease].

In 509 male patients, age less than 45 years, with angiographically documented coronary artery disease (CHD) we found (in contrast to age-matched controls: 459 participants of the PROCAM study) an increased amount of total cholesterol (259 vs. 221 mg/dl), LDL-cholesterol (185 vs. 142 mg/dl), Apo-B (138 vs. 118 mg/dl), lipoprotein(a) (12 vs. 5 mg/dl) and uric acid (6.4 vs. 5.8 mg/dl); HDL-cholesterol (40.5 vs. 46.8 mg/dl), Apo-A-I (122 vs. 143 mg/dl) and Apo-A-II (38 vs. 43 mg/dl) were significantly lower. These differences in lipid-metabolism between CHD-patients and controls in the younger group were essentially more pronounced than in older individuals of a group of 423 male patients over the age of 45 years who suffered from CHD and 545 age-matched PRO-CAM participants. Among the extent of the disorder in lipid metabolism, the apolipoprotein E-polymorphism, and the age of onset of CHD there exists a significant correlation which proves the special importance to therapeutically influence disorders of lipid metabolism especially in younger patients.

Adult↗
PubMed1991

A molecular defect causing fish eye disease: an amino acid exchange in lecithin-cholesterol acyltransferase (LCAT) leads to the selective loss of alpha-LCAT activity.

Epidemiological as well as biochemical evidence of recent years has established that a low plasma level of high density lipoprotein-cholesterol is a predictor for the risk of coronary artery disease. However, there is a heterogeneous group of rare familial disorders, characterized by severe high density lipoprotein deficiency, in which the predicted increased risk is not clearly apparent. One such disorder has been called fish eye disease to reflect the massive corneal opacification seen in these patients. In this report, we describe the biochemical and genetic presentation of two German fish eye disease homozygotes and their family members. Vertical transmission of a decrease in the specific activity of lecithin-cholesterol acyltransferase (EC 2.3.1.43) indicated that this enzyme was a candidate gene for harboring the defect responsible for this disorder. Direct sequencing of DNA segments amplified by the polymerase chain reaction (PCR) that encode the exons of the lecithin-cholesterol acyltransferase gene led to the identification of a homozygous mutation resulting in the substitution of threonine at codon 123 for an isoleucine residue in both individuals. Family analysis in an extended pedigree was used to establish a causal relationship between this mutation and the biochemical phenotype for fish eye disease. The homozygous presence of this mutation in two phenotypically homozygous members of an unrelated Dutch family with fish eye disease further supports this finding.

Aged↗
PubMed1991

Cloning, expression, and nucleotide sequence of rat liver sterol carrier protein 2 cDNAs.

The structure and expression of rat sterol carrier protein 2 (SCP2) were studied by cloning and sequencing SCP2 cDNAs and by hybridizing the SCP2 cDNA to RNA from a variety of rat tissues. Initial screening of a rat liver cDNA library with an oligonucleotide probe derived from the rat SCP2 protein sequence revealed an 825-base pair cDNA clone coding for the complete SCP2 protein sequence. Our results suggest that rat liver SCP2 is 143 amino acid residues long, including a 20-amino acid residue prepeptide (pre-SCP2). Using the rat SCP2 cDNA as a probe for Northern blot hybridization analyses under high stringency conditions with rat liver poly(A) RNA, four mRNA species differing in their sizes and levels of expression are detected. The lengths of the corresponding mRNAs are 0.8, 1.4, 2.1, and 2.7 kilobases (kb), respectively. In all other tissues analyzed mRNAs hybridizing to the SCP2 cDNA probe were detected in levels much lower than in the liver. In these tissues the vast majority of the expressed SCP2 mRNAs consists of the 0.8-kb mRNA. Results from Southern blotting hybridization analyses with rat genomic DNA suggest that the four different mRNA species are products of a single gene. Extensive screening of rat liver cDNA libraries using rat liver SCP2 cDNA probes led to the isolation of 10 additional clones, all of them containing cDNA insertions longer than 0.8 kb. Restriction mapping and nucleotide sequencing analyses of these cDNAs indicate that eight extend upstream of the SCP2 cDNA, and two extend 5' as well as 3'. Translation of the sequence extending most upstream suggests that this cDNA is a nearly full-length cDNA coding for a protein of 547 amino acids (SCP chi). SCP chi contains a 404-amino acid amino-terminal extension as compared with pre-SCP2 whereas its carboxyl-terminal part is identical with pre-SCP2. Sequencing of the 3' extension cDNAs suggests that polyadenylation had occurred 651 nucleotides downstream as compared with the remaining cDNAs. A probe from this region hybridizes to the 1.4- and 2.7-kb mRNAs. From our data we conclude that the 1.4- and 2.7-kb mRNA species are generated by alternative polyadenylation of the 0.8- and 2.1-kb mRNAs, respectively. In contrast, the 2.1- and 2.7-kb mRNAs contain an approximately 1300-nucleotide extension upstream of the 0.8- and 1.4-kb mRNAs, suggesting differential splicing of the primary SCP2 gene transcript leading to expression of pre-SCP2 and SCP chi from a single gene.

Amino Acid Sequence↗
PubMed1991

Molecular basis of lipoprotein lipase deficiency in two Austrian families with type I hyperlipoproteinemia.

To determine the molecular basis for type I hyperlipoproteinemia in two Austrian families, the lipoprotein lipase (LPL) gene of two patients exhibiting LPL deficiency was analyzed by Southern blotting and by direct genomic sequencing of DNA amplified by polymerase chain reaction (PCR). All exons of the LPL gene except part of the noncoding region of exon 10, all splice donor and acceptor sites, as well as 430 basepairs of the 5'-region including the promotor were sequenced. A homozygous substitution of adenine for guanine in the fifth exon at cDNA position 818 of the LPL gene was found in both patients. Our sequencing strategy largely ruled out a linkage disequilibrium of the identified nucleotide change with another defect potentially causing the clinical phenotype. The base change described abolishes a normally present AvaII restriction site allowing the identification of carriers of the mutant allele by AvaII digestion of PCR fragments of exon 5; three members of the two families were homozygous for this mutation and ten members were heterozygous. The activity of LPL in postheparin plasma was almost completely absent in homozygotes and about half normal in heterozygotes. The loss of activity was related to LPL protein structure. This mutation alters the amino acid sequence at residue 188 from Gly to Glu. The conformational preferences of the protein chain around position 188 were calculated with the use of a knowledge-based computerized method. The most probable conformation is a beta-turn formed by residues 189-192. The mutation seems to destabilize the beta-turn and/or a yet larger domain critical for substrate alignment.

Adult↗
PubMed1991

A frameshift mutation in the human apolipoprotein A-I gene causes high density lipoprotein deficiency, partial lecithin: cholesterol-acyltransferase deficiency, and corneal opacities.

Epidemiologic data of recent years have identified an important role of HDL deficiency in the etiology of atherosclerosis. Biochemical data suggest that some of these deficiencies may be a consequence of defects in the structural genes of HDL apolipoproteins or of plasma enzymes that modify HDL. We analyzed the genetic defect in a 42-yr-old patient suffering from corneal opacities and complete absence of HDL cholesterol but not of coronary artery disease, thus clinically resembling fish eye disease. The observation of an abnormal immunoblot banding pattern of apolipoprotein A-I (apo A-I) and of reduced lecithin: cholesterol acyltransferase (LCAT) activity in plasma led to sequence analysis of the genes for apo A-I and LCAT in this patient and his family. Direct sequencing of polymerase chain reaction amplified DNA segments containing the exons of the candidate genes, resulted in the identification of a frameshift mutation in apo A-I while the LCAT sequence was identical to the wild type. The apo A-I mutation was predictive for an extensive alteration of the COOH-terminal sequence of the encoded protein. Evidence for the release of this mutant protein into the plasma compartment and for the absence of normal apo A-I was derived from ultraviolet laser desorption/ionization mass spectrometry analysis. Our results suggest that a defective apo A-I is the causative defect in this case of HDL deficiency with corneal opacities.

Adult↗