Genetic analysis of indicators of cholesterol synthesis and absorption: Lathosterol and phytosterols in Dutch twins and their parents

Significant familial aggregation was observed for plasma levels of lathosterol (an indicator of whole-body cholesterol synthesis) and plant sterols campesterol and β-sitosterol (indicators of cholesterol absorption) in 160 Dutch families consisting of adolescent mono- and dizygotic twin pairs and their parents. For lathosterol a moderate genetic heritability in parents and offspring (29%) was found. In addition, shared environment also contributed significantly (37%) to variation in plasma lathosterol concentrations in twin siblings. However, a model with different genetic heritabilities in the two generations (10% in parents and 68% in offspring) fitted the data almost as well. For plasma plant sterol concentrations high heritabilities were found. For campesterol heritability was 80% and for β-sitosterol it was 73%, without evidence for differences in heritability between sexes or generations. No influence of common environmental influences shared by family members was seen for either campesterol or β-sitosterol. Taken together, these results confirm and expand the hypothesis that individual differences in plasma levels of noncholesterol sterols are moderately (lathosterol) to highly (plant sterols) heritable

The effect of tibolone on the lipoprotein profile of postmenopausal women with type III hyperlipoproteinemia

OBJECTIVE: To investigate the short-term effect of treatment with tibolone on plasma lipid and lipoprotein levels in postmenopausal women with type III hyperlipoproteinemia (HLP).DESIGN AND INTERVENTION: Patients were randomized to receive, in a double-blind cross-over fashion, a fixed dose of tibolone, 2.5 mg once daily or placebo for 8 weeks. The two treatment periods were separated by a wash-out period of 6 weeks. At each visit body weight and blood pressure were determined. Before and after each treatment period, fasting venous blood samples were obtained from the patients for biochemical measurements.SETTING: The Leiden University Medical Center.SUBJECTS: Postmenopausal women with type III HLP (aged ≤ 65 years) were recruited from the Lipid Clinics of the Leiden University Medical Center, the Amsterdam Medical Center, the Utrecht Medical Center and the University Hospital Rotterdam. Five out of 25 women with type III HLP were eligible to be included in the study. Four of the five included patients completed the study according to the protocol. One patient was excluded from blinded therapy because total cholesterol levels increased above 20 mmol L-1.MAIN OUTCOME MEASURES: A significant reduction of plasma triglyceride, total cholesterol, VLDL cholesterol and VLDL triglyceride levels.RESULTS: Plasma triglyceride and total cholesterol levels decreased from 6.82 +/- 3.58 to 2.45 +/- 1.36 mmol L-1 and from 13.53 +/- 3.64 to 6.61 +/- 2.03 mmol L-1, respectively (both P &lt; 0.05). The body mass index remained unchanged. The glycated haemoglobin percentage decreased significantly from 5.8 to 5.3%. Treatment with tibolone resulted in a profound reduction in plasma apolipoprotein E, VLDL cholesterol and VLDL triglyceride levels (mean reductions of 66, 77 and 70%, respectively, P &lt; 0.05).CONCLUSIONS: Tibolone is a valuable adjuvant to current therapy in postmenopausal women with type III HLP.</p

The effect of tibolone on the lipoprotein profile of postmenopausal women with type III hyperlipoproteinemia

OBJECTIVE: To investigate the short-term effect of treatment with tibolone on plasma lipid and lipoprotein levels in postmenopausal women with type III hyperlipoproteinemia (HLP).DESIGN AND INTERVENTION: Patients were randomized to receive, in a double-blind cross-over fashion, a fixed dose of tibolone, 2.5 mg once daily or placebo for 8 weeks. The two treatment periods were separated by a wash-out period of 6 weeks. At each visit body weight and blood pressure were determined. Before and after each treatment period, fasting venous blood samples were obtained from the patients for biochemical measurements.SETTING: The Leiden University Medical Center.SUBJECTS: Postmenopausal women with type III HLP (aged ≤ 65 years) were recruited from the Lipid Clinics of the Leiden University Medical Center, the Amsterdam Medical Center, the Utrecht Medical Center and the University Hospital Rotterdam. Five out of 25 women with type III HLP were eligible to be included in the study. Four of the five included patients completed the study according to the protocol. One patient was excluded from blinded therapy because total cholesterol levels increased above 20 mmol L-1.MAIN OUTCOME MEASURES: A significant reduction of plasma triglyceride, total cholesterol, VLDL cholesterol and VLDL triglyceride levels.RESULTS: Plasma triglyceride and total cholesterol levels decreased from 6.82 +/- 3.58 to 2.45 +/- 1.36 mmol L-1 and from 13.53 +/- 3.64 to 6.61 +/- 2.03 mmol L-1, respectively (both P &lt; 0.05). The body mass index remained unchanged. The glycated haemoglobin percentage decreased significantly from 5.8 to 5.3%. Treatment with tibolone resulted in a profound reduction in plasma apolipoprotein E, VLDL cholesterol and VLDL triglyceride levels (mean reductions of 66, 77 and 70%, respectively, P &lt; 0.05).CONCLUSIONS: Tibolone is a valuable adjuvant to current therapy in postmenopausal women with type III HLP.</p

The effect of the apolipoprotein E phenotype on plasma lipids is not influenced by environmental variability: results of a Dutch twin study

We tested the influence of the apolipoprotein E (apoE) polymorphism on the intrapair differences in the levels of plasma cholesterol, plasma triglycerides, low density lipoprotein-cholesterol, apoB and apoE in monozygotic (MZ) twins, and estimated whether or not there was a interaction between the apoE polymorphism and environmental factors. In 65 MZ twin pairs, the intrapair differences in the measured lipoprotein parameters were similar in the different apoE phenotype classes. This indicates that the effect of the apoE polymorphism is not influenced by environmental variability between the MZ pair members and accordingly identifies the APOE gene as a "level" gene. © 1993 Springer-Verlag

Expression of type III hyperlipoproteinemia in apolipoprotein E2 (Arg158 --> Cys) homozygotes is associated with hyperinsulinemia

Type III hyperlipoproteinemia (HLP) is mainly found in homozygous carriers of apolipoprotein E2 (apoE2, Arg158-->Cys). Only a small percentage (< 5%) of these apoE2 homozygotes develops hyperlipidemia, indicating that additional environmental and genetic factors contribute to the expression of type III HLP. In the present study, first, the prevalence of type III HLP among apoE2 homozygotes was estimated in a Dutch population sample of 8888 participants. Second, 68 normocholesterolemic and 162 hypercholesterolemic apoE2 homozygotes (type III HLP patients) were collected to investigate additional factors influencing type III HLP expression. In the Dutch population sample, apoE2 homozygosity occurred with a frequency of 0.6% (57 of 8888 individuals). Among the 57 E2/2 subjects, 10 type III HLP patients were identified (prevalence 18%). Comparison of normocholesterolemic E2/2 subjects and type III HLP patients showed that the latter had a significantly increased body mass index (25.6 +/- 4.0 versus 26.9 +/- 3.8 kg/m(2), respectively; P=0.03) and prevalence of hyperinsulinemia (26% versus 63%, respectively; P<0.001). Multiple linear regression analysis

Opsporing familiaire hypercholesterolemie bij kinderen geindiceerd? Bij uitzondering wel [Search for familial hypercholesterolaemia in children indicated? Only exceptionally]

De onderste leeftijdsgrens bij het opsporen van hypercholesterolemie in de standaard van het Nederlands Huisartsen Genootschap is 18 jaar.1 De (herziene) cholesterolconsensus uit 1991 geeft geen ondergrens aan.2 Familiaire hypercholesterolemie (FH)3 neemt een speciale plaats in, omdat het cardiovasculaire risico in bepaalde families buitensporig hoog kan zijn (zie het betoog van Bakker in dit nummer, bl. 2548). Veel familieleden van een probandus met FH weten niet dat de cholesterolconcentratie bij hen sterk verhoogd kan zijn. Nu er een werkzaam middel is om de prognose te verbeteren, lijkt opsporing van volwassenen met FH geen punt van discussie meer. Tegen opsporing van FH in de kinderleeftijd, door onderzoek van bloed, zijn echter bedenkingen aan te voeren