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Biomedical subjects

L U Gerdes

Publications and source records attributed to L U Gerdes.

At least 37 records · Page 2Linked to original sources
PubMed1997

Phenotypic variation in patients heterozygous for familial defective apolipoprotein B (FDB) in three European countries.

A glutamine-for-arginine substitution at amino acid position 3500 of apolipoprotein B (apo B) causes synthesis of LDL with reduced binding affinity to the LDL receptor (LDLR). The associated clinical syndrome has been named familial defective apolipoprotein B- 100 (FDB). In 205 FDB patients from Germany (n = 73). The Netherlands (n = 87), and Denmark (n = 45), we tried to assess determinants of variation in lipid concentrations. Besides age, sex, and geographic origin, variation in the LDLR gene was the most powerful determinant of variation in total cholesterol and LDL cholesterol levels. Polymorphic variation in the LDLR gene (SfaNI, exon 2; Nco I, exon 18) was associated with total cholesterol (TC) and LDL cholesterol (LDL-C) variation in women (SfaNI: P = .04 and .03 for TC and LDL-C, respectively; Nco I; P = .003 and .006, respectively), whereas the Ava II (exon 13) and the Pvu II (intron 15) polymorphisms were not. Combined information from all three LDLR exon polymorphisms showed that subjects with at least one S + A + N + allele had 13% to 20% higher TC than non-S + A + N + subjects (P = .02 [TC, men]; P = .01 [LDL-C, men]; P = .005 [TC, women]; and P = .004 [LDL-C, women]) and, together with age and geographic origin, accounted for 20% (women) and 19% (men) of the variation in LDL-C. The expected association of the apo E genotypes (e3e2, e3e3, and e3e4) with cholesterol concentrations was seen in S + A + N + but not in non-S + A + N + subjects and in P-P- but not in P + P + or P + P- subjects. With regard to clinical expression, FDB patients had lower TC and LDL-C levels and a lower prevalence of cardiovascular disease than 101 Danish patients with familial hypercholesterolemia.

Adult↗
PubMed1996

Effects of apoE gene polymorphism on Lp(a) concentrations depend on the size of apo(a): a study of 466 white men.

Polymorphisms in the genes for the low-density lipoprotein (LDL) receptor ligands, apolipoprotein E (apoE), and apolipoprotein B (apoB) are associated with variation in plasma levels of LDL cholesterol. Lp(a) lipoprotein(a) [Lp(a)] is LDL in which apoB is attached to a glycoprotein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined isoforms differing in molecular weight, which are inversely correlated with Lp(a) concentrations in blood. The interaction of apo(a) with triglyceride-rich lipoproteins differs with the size of apo(a), and therefore the effects of apoE gene polymorphism on Lp(a) levels could also depend on apo(a) size. We have investigated the possible effect of genetic variation in the apoE and apoB genes on plasma Lp(a) concentrations in 466 white men with different apo(a) phenotypes. Overall there was no significant association between the common apoE polymorphism and Lp(a), but in the subgroup with apo(a)-S4, concentrations of Lp(a) differed significantly among the apoE genotypes (P = 0.05). Lp(a) was highest in the apoE genotypes epsilon 2 epsilon 3 and epsilon 3 epsilon 3 and lowest in genotype epsilon 3 epsilon 4, and the apoE polymorphism was estimated to account for about 2.4% of the variation in Lp(a). In contrast, in the subgroup with apo(a)-S2 Lp(a) was significantly lower (P = 0.04) in apoE genotype epsilon 2 epsilon 3 than in genotype epsilon 3 epsilon 3. Lp(a) concentrations did not differ among the XbaI (P = 0.65) or SP 24/27 (P = 0.26) polymorphisms of the apoB gene. The expected effects of both apoE and apoB polymorphism on LDL levels were significant in the whole population sample and in subjects with large-sized apo(a) isoforms (P < 0.01), whereas no effect was seen in those with low molecular weight apo(a) isoforms. We conclude that the influence of apoE genotypes on Lp(a) concentrations depends on the size of the apo(a) molecule in Lp(a), possibly because both apo(a)-S4 and apoE4 have high affinity for triglyceride-rich lipoproteins and may be taken up and degraded rapidly by remnant receptors.

Apolipoproteins A↗
PubMed1996

Are men carrying the apolipoprotein epsilon 4- or epsilon 2 allele less fertile than epsilon 3 epsilon 3 genotypes?

The epsilon 3 allele in the human gene coding for apolipoprotein E (apoE) is the most common worldwide, but epsilon 4 is probably the ancestral allele. Since apoE is involved in many important biological processes, selection forces could have favoured epsilon 3. We hypothesized that apoE genotypes may affect reproductive efficiency, and we therefore compared the distributions of 40-year-old married men with known genotypes by the numbers of their biological children. The distributions were statistically significantly different (P = 0.0026). On average, men with the epsilon 3 epsilon 3 genotype (n = 212) had 1.93 children, men with the epsilon 3 epsilon 4 or epsilon 4 epsilon 4 genotype (n = 105) had 1.50, and men with the epsilon 3 epsilon 2 or epsilon 2 epsilon 2 genotypes (n = 53) had 1.66 children. Of the men in the three groups, 6%, 26% and 19%, respectively, reported being childless. These findings are unlikely to be due to gross error in the reported prevalence of childlessness, differences in socioeconomic status or other likely sources of bias. They are compatible with higher fertility in men with the epsilon 3 epsilon 3 genotype than in those with the other common apoE genotypes.

Adult↗
PubMed1996

The apolipoprotein E polymorphism in Greenland Inuit in its global perspective.

Apolipoprotein E (apoE) genotypes were determined in Inuit population samples from Nuuk on the south-west coast of Greenland (n = 100) and from the Ammassalik region on the south-east coast (n = 78). The epsilon 2 allele was absent in the latter sample, and the epsilon 4 allele frequency was relatively high, about 23%. As in most other populations, mean plasma lipoprotein-related variables, except high-density lipoprotein (HDL) cholesterol, were higher in both Inuit men and women with epsilon 4 than in epsilon 3 epsilon 3 genotypes (P < 0.05 for triglycerides in men, and for non-HDL cholesterol and apolipoprotein B in women). The estimated apoE allele frequencies were combined with data from other studies of aboriginal peoples to outline a world map of apoE allele frequencies. A recent study of non-human primates suggests that epsilon 4, and not epsilon 3, is the ancestral allele in humans and we have used the map to generate additional hypotheses regarding the history of the apoE polymorphism in humans.

Alleles↗
PubMed1995

Polymorphisms in the lipoprotein lipase gene and their associations with plasma lipid concentrations in 40-year-old Danish men.

BACKGROUND: In some previous studies, HindIII and Pvu II restriction fragment length polymorphisms (RFLPs) in the lipoprotein lipase (LPL) gene were associated with coronary heart disease and plasma concentrations of HDL cholesterol and triglycerides. However, the populations studied were relatively small and heterogeneous in regard to age, sex, and ethnic background. METHODS AND RESULTS: Associations of a HindIII (intron 8) and a Pvu II (intron 6) RFLP in the LPL gene with plasma concentrations of cholesterol, HDL cholesterol, non-HDL cholesterol, and triglycerides were studied in 457 randomly selected 40-year-old Danish men. The HindIII and the Pvu II sites were in strong linkage disequilibrium. The frequencies of the H+ and P+ alleles (+ denotes presence of cutting site) were 0.717 and 0.464, respectively. In multivariate analysis, there was a clear gene dosage effect of the H+ allele on HDL. The lowest HDL cholesterol concentration was in the H+H+ group, the highest concentration was in the H-H- group, and the H+H- group had intermediate HDL concentrations (P = .03). There was a similar, but not statistically significant gene dosage effect on triglyceride concentrations, with the highest value seen in the H+H+ group. There were no other associations between LPL RFLPs and lipoprotein components. In males reporting family history of premature ischemic heart disease, the H+H+ genotype was overrepresented (odds ratio, 2.75; 95% confidence interval, 1.37 to 5.53). CONCLUSIONS: The results suggest that genetic variation in or near the LPL gene plays a role in interindividual differences in HDL cholesterol concentration and in risk of atherosclerosis and ischemic heart disease in men.

Adult↗
PubMed1995

Apolipoprotein(a) phenotypes and lipoprotein(a) concentrations in patients with hyperthyroidism.

Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL) particle in which apolipoprotein B-100 (apoB) is attached to a glycoprotein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma are inversely correlated. High plasma levels of Lp(a) are associated with atherosclerotic diseases. It is therefore of interest to study whether factors other than the apo(a) gene locus are involved in the regulation of Lp(a) concentrations. We measured plasma concentrations of Lp(a) and other lipoproteins and determined apo(a) phenotypes in 31 patients with hyperthyroidism, before and after the patients had become euthyroid by treatment. The mean concentration of LDL cholesterol rose from 2.67 to 3.88 mmol/l (P < 0.01), apoB rose from 0.79 to 1.03 g/l (P < 0.01), and the median Lp(a) concentration increased from 9.74 to 18.97 mg/dl (P < 0.01) on treatment. Lp(a) concentrations were inversely associated to the size of the apo(a) molecule both before (P < 0.01) and after treatment (P < 0.01). The increase in Lp(a) was significant in patients with high molecular weight apo(a) phenotypes (n = 9; P < 0.01) and in patients with low molecular weight apo(a) phenotypes (n = 16; P < 0.01), but not in those with apo(a) "null types" (n = 6; P = 0.5). The low levels LDL cholesterol and apoB in untreated hyperthyroidism may result from increased LDL receptor activity. The increase in Lp(a) levels were not correlated with the increase in LDL cholesterol or apoB.(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoproteins↗
PubMed1995

A unique pattern of apo(a) polymorphism in an isolated east Greenlandic Inuit (Eskimo) population.

Eskimos of the east coast of Greenland very rarely had contacts with Caucasians until late in the 19th century. Their genes are therefore likely to be similar to those in the original Eskimo gene pool. We have compared serum concentrations of Lp(a) and apo(a) phenotypes in 78 East Greenland Eskimos (EGE) with those in Eskimos from Western Greenland (WGE) (n = 100) and Caucasian Danes (n = 466). Lp(a) levels were higher in EGE (median: 11.9 mg/dl [95% CI: 9.1-16.4]) than in Danes (p < 0.01), (median: 6.3 mg/dl [95% CI: 5.5-7.3]) and WGE (p < 0.01), (median: 7.8 mg/dl [95% CI: 5.7-10.2]). Lp(a) concentrations above 30 mg/dl were (p < 0.05) more common in EGE (19%) than in WGE (9%) and similar (p = 0.89) to those in Danes (20%). Apo(a) molecules as small as S2 or smaller (S1, B and F) were present in 26% of Danes and in 3% of WGE but were absent in EGE (p < 0.01). In contrast, a large apo(a) variant (VS4) was present in 54% of EGE and 62% of WGE, whereas it was very rare in Danes (2%). Lp(a) concentrations were inversely associated with apo(a) size in EGE (p < 0.05), WGE (p < 0.01) and Danes (p < 0.01), but EGE with S3 or S4 had significantly higher Lp(a) levels than Danes (p < 0.05) with the same phenotypes.

Adolescent↗
PubMed1995

Hypocholesterolaemic effect of a new fermented milk product in healthy middle-aged men.

OBJECTIVE: There are still controversies as to the potential beneficial effects of milk and fermented milk products on the level of lipoproteins. The objective of the present investigation was to test the effect of a moderate daily intake of a new fermented milk product, which was based on a bacterial culture obtained from the intestinal flora of inhabitants of Abkhasia, on the lipoprotein levels of a homogeneous group of middle-aged Danish men. DESIGN: The study was randomised, double-blind, and placebo-controlled, and the intervention was performed for a period of 6 weeks. SUBJECTS: Fifty-eight healthy, non-obese, normocholesterolaemic, male volunteers born in 1949 of Danish descent participated (i.e. all were 44 years old). INTERVENTIONS: During the intervention period the subjects' habitual diets were supplemented with 200 ml/day of either the new fermented milk product or a placebo product (chemically fermented). The biologically fermented milk product contained Enterococcus faecium and two strains of Streptococcus termophilus. Fasting blood samples were drawn initially and after 3 and 6 weeks and analysed for plasma values of total cholesterol, high-density lipoprotein (HDL)-cholesterol and triglyceride. In addition, LDL-cholesterol was estimated. RESULTS: After these 6 weeks total cholesterol was reduced significantly in the group given biologically fermented milk (-0.37 mmol/l, confidence interval: -0.51 to -0.23) while no changes were observed in the placebo group (-0.02 mmol/l) (P < 0.01). This reduction in total cholesterol could be completely ascribed to a fall in LDL-cholesterol by 10% (i.e. -0.42 mmol/l) since HDL-cholesterol and triglyceride were unchanged in both groups. CONCLUSIONS: Thus, this short-term study (6 weeks) demonstrated an LDL-cholesterol-lowering effect (10% reduction) of a new fermented milk product in middle-aged Danish men.

Adult↗
PubMed1994

Incidence of the apolipoprotein B-3500 mutation in Denmark.

A total of 5000 consecutively samples newborn screening cards were anonymously selected for screening for the apolipoprotein B-3500 (apo B-3500) mutation, which causes familial defective apolipoprotein B-100 (FDB). The mutation was found in 5 of 5000 Danish children, of whom 2 were twins. This indicates a lower prevalence of this mutation in Danes than that reported in the UK, Germany, USA, Austria, Canada and especially Switzerland. Haplotype studies suggest that Caucasian subjects with the apo B-3500 mutation have a common founder. The apparently lower prevalence in Denmark than in Switzerland and Central Europe may indicate that the mutation was brought from these areas to Denmark after the initial settling of Denmark. In 101 unrelated Danish subjects with familial hypercholesterolemia, diagnosed on clinical and biochemical criteria including tendon xanthomata, 2 were heterozygous for the apo B-3500 mutation (2%).

Apolipoproteins B↗
PubMed1994

Genotyping compared with protein phenotyping of the common apolipoprotein E polymorphism.

Apolipoprotein E (apo E) genotypes have been determined in 460 Danish men, with the use of the polymerase chain reaction (PCR) to amplify a 244 base pair fragment spanning the first-base polymorphic sites in the codons of amino acids 112 and 158 followed by restriction endonuclease cleavage. The results were compared with the apo E phenotypes previously determined by isoelectric focusing (IEF) of delipidated plasma, not pretreated with neuraminidase, followed by apo E specific immunoblotting. Conflicting results were found in only 9 cases (2.0%) and in each case only with respect to one allele. Five of the discrepancies can be explained, post hoc, by technical difficulties with the IEF method ('faint bands'). A possible cause of the other 4 discrepancies is the presence of rare mutations. Our findings in this large study are reassuring, since, if appreciable and systematic misclassification of genotypes do occur by using IEF, as has been reported from some laboratories, it may influence the validity of genetic epidemiological studies.

Adult↗
PubMed1994

Treatment of patients with familial defective apolipoprotein B-100 with pravastatin and gemfibrozil: a two-period cross-over study.

Thirty patients with familial defective apolipoprotein B-100 were treated in a two-period (8 weeks each) cross-over study with pravastatin and gemfibrozil. Cholesterol, LDL cholesterol, and apo B were reduced by 20-25% (P < 10(-4)) by pravastatin and by 4-6% by gemfibrozil (pravastatin vs. gemfibrozil: P < 10(-4)). Response to pravastatin was variable and not correlated to gender, age, or apo E genotype. Gemfibrozil lowered triglycerides by 25% (P < 10(-4)) and raised HDL cholesterol by 11%. The effects of pravastatin on these two interrelated variables were significantly smaller. Both drugs increased Lp(a) significantly by about 10%. The LDL cholesterol lowering effect of pravastatin in patients with FDB is similar to that observed in patients with familial hypercholesterolemia.

Adult↗
PubMed1994

Apolipoprotein B gene polymorphisms in ischemic heart disease and hypercholesterolemia: effects of age and sex.

The association of polymorphic alleles of the apolipoprotein B gene (Insertion/Deletion-, XbaI-, MspI-, EcoRI-, and 3'-VNTR polymorphisms) with variation in lipid concentrations (total cholesterol (T-C), HDL cholesterol (HDL-C), and log-triglycerides (TG)) in plasma was studied in 259 men and 59 women with moderate hypercholesterolemia (T-C 5.5-8.0 mmol/l and TG < 2.5 mmol/l) and ischemic heart disease, especially in relation to the effect of sex and age. The XbaI and the Ins/Del polymorphic alleles were associated with variation in T-C, but only in patients below the 75th percentile for age. The XbaI and Ins/Del polymorphic alleles were synergistically associated with variation in T-C: the X+ and the Del alleles were associated with higher cholesterol concentrations. Younger male patients had the highest frequency of haplotypes including both the X+ and the Del alleles, but the most striking difference was a significantly higher frequency of haplotypes including both the X- and the Ins alleles in female and in older male patients. The heterogeneity of association of polymorphic alleles in the apolipoprotein B gene to complex traits like hypercholesterolemia and ischemic heart disease in this study could explain why in most studies the X+ allele has been associated with higher cholesterol levels, whereas the X- allele has been associated with symptomatic atherosclerosis. The results of our study emphasize the importance of age and sex in measured genotype association studies.

Adult↗
PubMed1993

[Cholesterol-lowering effect of a new fermented milk product in healthy 44-year old Danish men].

The potential cholesterol-lowering effect of a new fermented milk product was tested in a homogeneous group of Danish men (all 44-year-old; n = 58) in a randomised, double blinded and placebo-controlled study. Two hundred ml of the fremented milk or placebo (chemically acidified) was taken daily for six weeks. After these six weeks total cholesterol decreased significantly in the fermented milk group by -0.37 mmol/l (confidence interval: -0.51 to -0.23 mmol/l) and no changes were observed in the placebo group (-0.02 mmol/l) (p < 0.01). This decrement in total cholesterol could be completely ascribed to a reduction of LDL-cholesterol by 10% (i.e. -0.42 mmol/l), since HDL-cholesterol and triglyceride were unchanged in both groups during the study. Thus, in the present short term study, the tested fermented milk product was able to reduce LDL-cholesterol in middle-aged men.

Adult↗
PubMed1993

A PvuII polymorphism of the low density lipoprotein receptor gene is not associated with plasma concentrations of low density lipoproteins including LP(a).

Lipoprotein(a) [Lp(a)] is a low density lipoprotein (LDL), in which apolipoprotein B-100 (apo B-100) is attached to apolipoprotein(a) [apo(a)], a glycoprotein of variable size. Lp(a) may be as atherogenic as LDL. In normal populations, Lp(a) concentrations in plasma are largely determined by the apo(a) gene locus on chromosome 6, but regulation of synthesis and catabolism of Lp(a) is poorly understood. In some studies, a PvuII restriction fragment length polymorphism (RFLP) in the LDL receptor gene seems to affect concentrations of LDL in plasma, and other studies have indicated that Lp(a) catabolism could be mediated by the LDL receptor. We therefore expected that the PvuII polymorphism in the LDL receptor gene might be associated with Lp(a) levels in 170 Caucasian men aged 40 years, selected to have a high representation of low molecular weight apo(a) phenotypes. However, plasma concentrations of cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides and Lp(a) were all unrelated to the LDL receptor gene PvuII polymorphism both in the group as a whole and when it was subgrouped by apo(a) phenotype. Therefore our data do not support the concept that this particular LDL receptor gene polymorphism is associated with LDL receptor function, and our data therefore neither support nor rule out a role for the LDL receptor in Lp(a) catabolism.

Adult↗
PubMed1993

Polymorphisms in the apolipoprotein B-100 gene contributes to normal variation in plasma lipids in 464 Danish men born in 1948.

We have studied the possible association of 5 polymorphisms in the apoB gene [a 9-bp insertion/deletion length polymorphism in the signal peptide coding region, XbaI, MspI, and EcoRI restriction fragment length polymorphisms (RFLPs) and a 15-bp variable number of tandem repeats (VNTR) region 3' to the apoB gene] with plasma concentrations of cholesterol, high density lipoprotein cholesterol, triglycerides and apolipoprotein B-100 in 464 randomly selected Danish men born in 1948. The XbaI RFLP and the insertion/deletion length polymorphism were significantly associated with plasma concentration and inter-individual variation of cholesterol and apolipoprotein B-100 (1.77% and 1.37% of sample variance in cholesterol, and 1.4% and 1.39% of sample variance in apoB). The association was particularly strong in men with a body mass index less than 25 kg/m2 (the mean value of the whole cohort) (3.43% and 2.93% of sample variance in cholesterol, and 3.1% and 2.13% of sample variance in apoB). The XbaI RFLP and the insertion/deletion length polymorphism were in strong linkage disequilibrium, explaining why independent associations of these two polymorphisms with cholesterol and apoB could not be established. There were no other associations between apoB gene polymorphisms and lipoprotein components.

Alleles↗
PubMed1993

Genetic markers in the apo AI-CIII-AIV gene cluster for combined hyperlipidemia, hypertriglyceridemia, and predisposition to atherosclerosis.

The aim of the present study was to search for genetic determinants of combined hyperlipidemia and hypertriglyceridemia, and to evaluate whether such determinants might be associated with predisposition to atherosclerosis. Four DNA polymorphisms in the apo AI-CIII-AIV gene cluster (G to A mutation at position -75 basepairs in the apo AI promoter, XmnI, PstI and SstI) were studied in relation to combined hyperlipidemia, hypertriglyceridemia, lipoprotein levels, atherosclerosis and age in 221 Danish men. The frequency of the rare allele of the XmnI polymorphism, the X+ allele, was higher in individuals below 55 years of age with combined hyperlipidemia than in individuals with normal lipid levels (0.31 vs. 0.14; P = 0.05). The rare allele of the SstI polymorphism, the S+ allele, was more frequent in hypertriglyceridemic individuals compared with normotriglyceridemic individuals (0.16 vs. 0.09; P < 0.05) and on analysis of variance the combined S-S+ and S+S+ genotypes were also associated with the highest triglyceride levels. Furthermore, the frequency of the S+ allele decreased significantly as a function of age in nonatherosclerotic subjects (from 0.15 to 0.10 to 0.02 in 48-, 63- and 85-year-olds, respectively; 48- versus 85-year-olds, P = 0.03). These results suggest that genetic variation in the apo AI-CIII-AIV gene complex is associated with combined hyperlipidemia and hypertriglyceridemia and may have an impact on longevity and/or predisposition to atherosclerosis.

Aged↗