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  • 1
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Familial combined hyperlipidemia (FCHL), characterized by elevated levels of serum total cholesterol, triglycerides or both, is observed in about 20% of individuals with premature coronary heart disease. We previously identified a locus linked to FCHL on 1q21–q23 in Finnish families with the ...
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] More than half of the patients with angiographically confirmed premature coronary heart disease (CHD) have a familial lipoprotein disorder1. Familial combined hyperlipidaemia (FCHL) represents the most common genetic dyslipidemia with a prevalence of 1.0–2.0% (refs 2,3). FCHL is estimated to ...
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  • 3
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary The associations between four restriction fragment length polymorphisms (RFLPs) of the gene for human apolipoprotein B (apo B) and five antigen group (Ag) protein-polymorphisms of apo B have been investigated in 24 unrelated Finnish individuals. In this sample a complete correlation exists between the EcoRI RFLP and the Ag(t/z) polymorphism. There is strong association between the alleles of the XbaI RFLP and Ag(c/g) and a weaker one of the same XbaI site with Ag(x/y). Linkage disequilibrium is observed between the PvuII RFLP and the Ag(a1/d) polymorphism. These associations confirm that the Ag variants are true protein sequence polymorphisms of apo B.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Earlier we reported that allelic variation in the gene coding for apolipoprotein (apoE) is a significant predictor of variation in the risk of coronary heart disease (CHD) death in a longitudinal study of elderly Finnish men. Here we address the question: which of the apoE genotypes confers the risk information in these men, and whether such information persists after other CHD risk factors are considered? We followed two cohorts of elderly Finnish men aged 65 to 84 years, one in Eastern (n = 281) and the other in the Southwestern (n = 344) Finland for 5 years during which 26 (9.3%) of the men from the Eastern cohort and 40 (11.6%) of the men in the Southwestern cohort died from CHD. Baseline high density lipoprotein (HDL) cholesterol and (HDL cholesterol)2 in the Eastern cohort and age, and total and HDL cholesterol and smoking status in the Southwestern cohort were significant predictors of CHD death (P 〈 0.05). The apoE genotypes were significant predictors in the Southwestern cohort atP = 0.02 and in the Eastern cohort atP = 0.18. In multivariable models, information about apoE genotypes improved the prediction atP = 0.10 level of statistical significance in both cohorts. When genotypes were considered separately, the ε2/4 combined with the ε4/4 in the Eastern cohort (odds ratio = 7.69, 95% CI = 1.67-35.52) and the ε3/4 in the Southwestern cohort (odds ratio = 2.44, 95% CI = 1.16–5.10) had sigificanctly greater odds of CHD death compared to the common ε3/3 genotype. We conclude that apoE genotypes confer risk information about CHD death in two cohorts of elderly Finnish men in a longitudinal study, and this information persists after adjustment for other CHD risk factors. Because different genotypes were predictors in these two cohorts, we further conclude that the utility of a particular genotype as a predictor of CHD death in other populations may depend on the distribution of risk factor profiles at baseline, geographically defined environmental exposures, the CHD mortality history, and the evolutionary history of background genotypes in the population considered.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Human genetics 〈Berlin〉 87 (1991), S. 657-660 
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Determination of paternity was attempted in the case of three children whose putative fathers are dead using DNA samples of the paternal grandparents. The DNA analyses were performed with both multilocus and single-locus probes which resolve highly polymorphic areas of human genome. The results were conclusive with both types of probes and facilitated, for example, the exclusion of the brother of the putative father. The evidence for true paternity obtained with DNA analyses can be considered reliable in this type of “indirect” paternity in which tests based on protein polymorphism are inconclusive.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Earlier we reported that allelic variation in the gene coding for apolipoprotein (apoE) is a significant predictor of variation in the risk of coronary heart disease (CHD) death in a longitudinal study of elderly Finnish men. Here we address the question: which of the apoE genotypes confers the risk information in these men, and whether such information persists after other CHD risk factors are considered? We followed two cohorts of elderly Finnish men aged 65 to 84 years, one in Eastern (n = 281) and the other in the Southwestern (n = 344) Finland for 5 years during which 26 (9.3%) of the men from the Eastern cohort and 40 (11.6%) of the men in the Southwestern cohort died from CHD. Baseline high density lipoprotein (HDL) cholesterol and (HDL cholesterol)2 in the Eastern cohort and age, and total and HDL cholesterol and smoking status in the Southwestern cohort were significant predictors of CHD death (P 〈 0.05). The apoE genotypes were significant predictors in the Southwestern cohort at P = 0.02 and in the Eastern cohort at P = 0.18. In multivariable models, information about apoE genotypes improved the prediction at P = 0.10 level of statistical significance in both cohorts. When genotypes were considered separately, the ɛ2/4 combined with the ɛ4/4 in the Eastern cohort (odds ratio = 7.69, 95% CI = 1.67–35.52) and the ɛ3/4 in the Southwestern cohort (odds ratio = 2.44, 95% CI = 1.16– 5.10) had sigificanctly greater odds of CHD death compared to the common ɛ3/3 genotype. We conclude that apoE genotypes confer risk information about CHD death in two cohorts of elderly Finnish men in a longitudinal study, and this information persists after adjustment for other CHD risk factors. Because different genotypes were predictors in these two cohorts, we further conclude that the utility of a particular genotype as a predictor of CHD death in other populations may depend on the distribution of risk factor profiles at baseline, geographically defined environmental exposures, the CHD mortality history, and the evolutionary history of background genotypes in the population considered.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary We determined TaqI-A, TaqI-B and EcoNI genotypes at the cholesteryl ester transfer protein (CETP) locus in 111 healthy volunteers and in 187 hyperlipidemic men of whom 72 had suffered a myocardial infarction. There were no significant differences in the allele distributions at these polymorphic loci either between the population sample and the hyperlipidemic subjects, or between patients with and without previous myocardial infarction. To detect the associations between the CETP polymorphisms and serum lipid and apoprotein levels, we determined the serum concentrations of total cholesterol, triglycerides, high density lipoprotein (HDL)-cholesterol, apoA-I, apoA-II and apoB in the subjects studied and correlated them to the 3 RFLPs. No significant differences were observed in the serum levels of apoproteins and lipid parameters between subjects with different genotypes in any of these polymorphic CETP loci, either in the population sample or in hyperlipidemic men. Multivariate analyses did not reveal a significant independent role for any of the 3 polymorphisms in determining serum HDL-cholesterol or apoA-I levels after adjusting for triglyceride and low density lipoprotein cholesterol concentrations. This was evident for the group of healthy volunteers and for hyperlipidemic subjects, including those who had survived a myocardial infarction. We conclude that, in Finns, the CETP RFLPs are not useful markers for the risk of coronary heart disease.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Human genetics 〈Berlin〉 90 (1992), S. 193-193 
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1573-7284
    Keywords: Elderly ; Health-status ; Insulin ; Lipids ; Metabolic-syndrome ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The clinical significances of different components of the multiple metabolic syndrome were studied in a five-year follow-up study of random persons (n = 1,199) of four birth cohorts at ages 65, 75, 80, and 85 years. The subjects were examined clinically and their serum lipids, blood glucose, plasma insulin, blood pressure, and health score were determined. The health score was measured using a visual analogue scale. All subjects were followed for 5 years. Health score, diastolic blood pressure and body mass index declined over age, but serum triglycerides, and blood glucose were similar, whilst serum high density lipoprotein (HDL)-cholesterol increased. Among women fasting plasma insulin was lowest in the age group of 65 years. The associations of components of the multiple metabolic syndrome varied by age. In the age groups of 65 and 75 years high body mass index, plasma insulin, glucose, triglycerides and low HDL-cholesterol were associated with impaired health. In the age group of 85 years high blood pressure, total cholesterol, and HDL-cholesterol were associated with good health. The baseline health score was consistently lower in the decedents than survivors of all age groups, but components of the metabolic syndrome were generally not associated with impaired survival.
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  • 10
    ISSN: 1432-0878
    Keywords: Adrenal cortex ; Differentiation ; Tissue culture ; Mevinolin ; Steroids ; Ultrastructure ; Rat (Sprague-Dawley)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Summary Mevinolin, an inhibitor of cholesterol synthesis, was used to study the effect of endogenous cholesterol synthesis on the morphology and function of differentiating and differentiated fetal rat adrenocortical cells grown in primary culture. Upon adrenocorticotrophic hormone (ACTH) stimulation under conditions in which endogenous cholesterol synthesis was inhibited but exogenous (lipoprotein) cholesterol was available, the cells differentiated normally from glomerulosa-like to fasciculata-like cells; the steroid hormone secretion was maximally induced. Under conditions in which cholesterol synthesis was maximally inhibited by mevinolin and the cells had no access to exogenous cholesterol, the cells did not differentiate into fasciculata-like cells; the ACTH-induced steroid response was highly suppressed under these conditions. The addition of either human low-density lipoprotein (LDL) or high-density lipoprotein (HDL3) to the culture medium restored the ACTH-induced differentiation and steroid secretion. Thus, in the absence of exogenous cholesterol, endogenous cholesterol synthesis was a prerequisite for differentiation. In cultures grown in the presence of exogenous cholesterol and ACTH with mevinolin-inhibited cholesterol synthesis and high steroid output, an increase in cytoplasmic lipids was evident, suggesting upregulation of LDL and HDL receptors. The results also demonstrated that induction of phenotypic differentiation from glomerulosalike into fasciculata-like cells can proceed in the presence of a cholesterol synthesis inhibitor like mevinolin; this differentiation in the absence of endogenous cholesterol synthesis is accompanied by the appearance of cytoplasmic cholesterol ester droplets, typical of fasciculata cells.
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