Apolipoprotein E/intrauterine undernutrition interaction and hypercholesterolemia in children.

The inconsistency of data regarding intrauterine programming of cardiovascular risk factors may be largely caused by genetic predisposition and later lifestyle. We analyzed whether low birth weight and apolipoprotein E (Apo E) polymorphism participate in the onset of hypercholesterolemia in children. Our approach was based on hypothesis that genetically enhanced susceptibility of different individuals might influence the effects of intrauterine programming. Two groups were selected from 2000 children at the beginning of an ongoing study: high-cholesterol group (HCG, n=67) and low-cholesterol group as a control (LCG, n=72). Both groups were divided into tertilles according to birth weight and we compared birth weight and apo E gene polymorphism between and within groups. The birth weight in HCG was 0.3 kg lower than the controls (p<0.001). The frequency of apoE4 was 31 % in HCG and only 10 % in LCG. The frequency of apoE4+ genotypes was not significantly different between tertilles based on birth weight in HCG. We suppose that intrauterine undernutrition, demonstrated by a lower birth weight, participates in the development of hypercholesterolemia already in childhood. The effects of low birth weight and the candidate gene - apoE, are synergic.

[Antagonistic effect of the insertion/deletion (HpaI) polymorphism in the regulatory part of the gene for apolipoprotein CI in children with high and low levels of cholesterol]. / Protichudný efekt inzercního/delecního (HpaI) polymorfizmu v regulacní cásti genu pro apolipoprotein CI u detí s vysokou a nízkou hladinou cholesterolu.

BACKGROUND: High plasma lipids are one of the risk factor of atherosclerosis. Both environmental (diet, physic activity) and genetic factors have been implicated in the development of hyperlipidaemia. Apolipoprotein (apo) CI plays an important role in plasma cholesterol and triglycerides transport by VLDL particles. The aim of the study was to establish the role of the insertion/deletion polymorphism in apoCI gene in the determination of plasma lipids in children. METHODS AND RESULTS: Using PCR and restriction analysis (HpaI) we have measured I/D polymorphism in APOCI gene in two groups of children selected from opposite ends of the cholesterol distribution curve of 2000 children. Eighty-two children in high-(HCG) and eighty-six children in low-(LCG) cholesterolemic groups participated on the study. No significant difference was found in the frequencies of the APOCI genotypes or alleles between HCG vs. LCG. Association between LDL cholesterol and genotypes within the LCG was found--the D/D homozygotes have higher lipid level compared to the others (p < 0.05). In LCG opposite, but insignificant (p = 0.09) trend was observed. CONCLUSIONS: The widespread I/D polymorphism in the gene for APOCI determines the plasma lipid levels in childhood and it could become another important genetic marker that plays a role in the genetic determination of cholesterolemia.

[Polymorphism in the regulatory part of the cholesterol 7 alpha hydroxylase gene in children with high and low levels of cholesterol]. / Polymorfizmus v regulacní cásti genu pro cholesterol 7 alpha hydroxylázu u detí s vysokou a nízkou hladinou cholesterolu.

BACKGROUND: High plasma cholesterol is one of the risk factors of atherosclerosis. Both environmental (diet, physic activity) and genetic factors have been concerned in the development of hypercholesterolemia. Cholesterol 7 alpha hydroxylase (CYP-7A1) is a key enzyme in the bile acid synthesis and it plays an important role in cholesterol catabolism. The aim of the study was to establish the role of A-204-->C polymorphism in CYP-7A1 gene in plasma lipid determination in children. METHODS AND RESULTS: Using PCR and restriction analysis (BsaI) we have measured A-204-->C polymorphism in CYP-7A1 gene in two groups of children selected from opposite ends of the cholesterol distribution curve of 2000 children. Eighty-two children in high- (HCG) and eighty-six children in low- (LCG) cholesterolemic groups participated in the study. No significant difference was found in the frequencies of the genotypes or alleles of the A-204-->C polymorphism in the CYP-7A1 gene between HCG and LCG. In HCG, C/C-204 homozygotes have the highest and A/A homozygotes the lowest levels of LDL-cholesterol (4.21 +/- 0.68 mmol/l vers. 3.69 +/- 0.60 mmol/l, p < 0.05). No associations between lipid parameters and genotypes within the LCG group were found. CONCLUSIONS: The A-204-->C polymorphism in the gene for CYP-7A1 is not the major determinant of plasma lipid levels in childhood. Its impact is expressed only on high cholesterol background.

Association between apolipoprotein B promotor haplotypes and cholesterol status.

Association between apolipoprotein B (apo B) promoter haplotypes and cholesterol concentration was studied in two groups of children with low and high concentrations of cholesterol. Strong linkage equilibrium was demonstrated between I/D in the signal peptide of apo B and (C-516T) polymorphism in the promotor of apo B gene, and the I/I+ allele T haplotype was associated with a low cholesterol concentration.

[Polymorphisms in genes for cholesterol ester transfer protein, apolipoprotein C-III and lipoprotein lipase in children with high and low cholesterol levels] ]. / Polymorfizmy v genech pro cholesterol ester transferový protein, apolipoprotein CIII a lipoproteinovou lipázu u detí s vysokou a nízkou hladinou cholesterolu.

BACKGROUND: High plasma lipids are one of the risk factor of atherosclerosis. The contribution of environmental and genetic factors to plasma lipids is roughly equal. Cholesterol ester transfer protein (CETP), lipoprotein lipase (LPL) and apolipoprotein (apo) CIII play an important role in plasma lipid metabolism. The aim of the study was to establish the role of polymorphisms in these genes in plasma lipid determination. METHODS AND RESULTS: Using PCR and restriction analysis we have measured Taq1 polymorphism in CETP, asparagine 291/serine polymorphism in LPL and C3238G polymorphism in apo CIII genes in two groups of children selected from opposite ends of the cholesterol distribution curve of 2000 children. 82 children in high- (HCG) and 86 in low- (LCG) cholesterol group participated in the study. No significant difference was found in the frequencies of the CETP and apo CIII genotypes between LCG and HCG. In the LCG, significantly more carriers (p < 0.05) of the LPL serine291 allele were found. CONCLUSIONS: Common polymorphisms in the CETP and apo CIII genes do not determine the plasma lipid levels in childhood. The carriers of the rare allele in the LPL gene could be genetically predisposed to low plasma lipid levels.

Low birth weight, apolipoprotein B Xba I polymorphism and hypercholesterolemia in childhood.

BACKGROUND: Xba I polymorphism in the apolipoprotein (apo) B gene has often been studied in connection with myocardial infarction, coronary artery disease and plasma lipid concentrations. The X2 allele (restriction site present) is often mentioned as a disadvantageous one. Low birth weight has also been described as a risk factor for hyperlipidemia. OBJECTIVE: To study the Xba I polymorphism in the apo B gene. PATIENTS AND METHODS: Southern blot or polymerase chain reaction was used in two groups of children (low and high cholesterolemic, 82 and 86 children, respectively), selected from 2000 children with known birth weight. RESULTS: In the subgroup of high cholesterolemic children with birth weight under 3.00 kg, the X1/X1 (P=0.056) genotype was found at a lower frequency. No similar association was shown in low cholesterolemic children. CONCLUSION: Xba I polymorphism is in a strong linkage disequilibrium with Ala (591) --> Val polymorphism in apo B, which influences postprandial lipemia and so, possibly, intrauterine nutrition and, consequently, birth weight. These results suggest that, in lower birth weight probands, X1/X1 homozygosity of Xba I polymorphism in the apo B gene may protect against the development of hypercholesterolemia, at least in childhood.

[Development of smoking habits in the population of the Czech Republic from 1985 to 1997/98]. / Vývoj kuráckých zvyklostí obyvatelstva Ceské republiky v období 1985-1997/98.

BACKGROUND: Tobacco smoking belongs to high risk factors for the circulation diseases. Aim of the present study is to identify and describe smoking habits of the population in nine districts in Czech republic in years 1997/98 and in six of these districts to analyze smoking trends during the period of 1985-1997/98. METHODS AND RESULTS: Information on the smoking habits were collected in years 1985, 1988, and 1992 in six districts which took part in the international project WHO MONICA. In 1997/98 data collection was extended into three other districts. New randomly selected samples of 1% of the population were explored each time. 5293 males and 5610 females 25-64 years old were questioned during a controlled talk with a health-officer. In 1997/98 in nine districts the prevalence of actual smokers was 38%, that of former smokers was 24% and 38% of non-smokers. The group of females consisted of 27% of actual smokers, 10% of former smokers, and 63% of non-smokers. The average daily consumption was 16.4% (+/- 8.6) cigarettes per day in males and 11.3 (+/- 7.0) cigarettes per day in females. In 1985-1997/98 the smoking prevalence of males aged 25-64 years decreased in six districts from 49% to 37% (p < 0.001). No changes were detected in females of the same age group (28% in 1985, 26% in 1997/98). Decreasing tendency was observed in both males and females up to 45 years old, in males also in the age group 55-64 years. In females older than 45 years the smoking prevalence increased. Significant changes in the smoking prevalence were found when samples were analyzed according to the education level. In males with basic education and among skilled workers the smoking prevalence decreased in years 1985-1997 from 53% to 42% (p < 0.05), among males with secondary education smoking prevalence decreased from 45% to 33% (p < 0.01) and in graduates from 34% to 23% (p < 0.01). In females with basic education the smoking prevalence increased from 25% to 31% (p < 0.05), among females with secondary education it decreased from 34% to 21% (p < 0.001), in graduate females it decreased from 31% to 18% (p < 0.05). CONCLUSIONS: Present situation and 13 years long development of smoking habits differs in males and females. Higher prevalence was found in males as well as the daily consumption of cigarettes. Since 1985 the male smoking prevalence has decreased in age groups 25-64 years and in age and education level subgroups. Only partial decrease of the female smoking prevalence was observed in age group till 45 years and in subgroups with secondary education and graduates. Significant increase in the smoking prevalence among females with basic education as well as the finding that women do not quit smoking with increasing age my become an important information for preventive programmes.

(TTA)n repeat polymorphism in the HMG-CoA reductase gene and cholesterolaemia.

BACKGROUND: Hypercholesterolaemia is one of the main risk factors of atherosclerosis. Both environmental and genetic factors have been implicated in the development of hypercholesterolaemia. The enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase plays an important role in cholesterol synthesis. Thus we supposed that polymorphisms in this gene could influence cholesterolaemia. PATIENTS AND METHODS: Using PCR, we measured the (TTA)n repeat polymorphism near the Alu sequence of the gene for HMG-CoA reductase in two groups of children selected from opposite ends of the cholesterolaemia distribution curve obtained from measuring cholesterolaemia in 2000 children. Eighty-two children in high- and eighty-six children in low-cholesterolaemic groups participated on the study. RESULTS: A significant difference was found in the frequencies of the genotypes of the 10+ add alleles (43.9% in high-cholesterolaemic children vs 24.4% in low-cholesterolaemic children p < 0.025). No differences were demonstrated in the frequencies of other genotypes (allele 10+ even and without allele 10). No associations between lipid parameters and genotypes or genotype subgroups within the group of high- and low-cholesterolaemic children were found. CONCLUSION: The (TTA)n repeat polymorphism in the gene for HMG-CoA reductase could be another genetic marker that plays a role in the genetic determination of cholesterolaemia.

Lack of an association between apolipoprotein B XbaI polymorphism and blood lipid parameters in childhood.

The frequencies of the alleles of XbaI polymorphism in the apolipoprotein B gene were determined in two groups of children, 82 with high (HCG) and 86 with low (LCG) cholesterol levels. A slightly higher incidence of the X2X2 genotype in HCG was found, but the differences were not statistically significant. No relations were found between the XbaI polymorphic site and the levels of serum lipids and lipoproteins. Common XbaI polymorphism in the apolipoprotein B gene does not determine significantly the plasma cholesterol levels in childhood.

Genetic markers in hypercholesterolemic and normocholesterolemic Czech children.

The genetic background of polygenic hypercholesterolemia was studied in hypercholesterolemic children consuming a diet identical to control individuals with low cholesterol concentrations. Significantly higher frequencies of "disadvantage" alleles, usually combined with a higher LDL cholesterol, were found in hypercholesterolemic individuals when polymorphisms in apolipoprotein E, apolipoprotein B--XbaI and LDL receptor--PvuII were studied.

[Serum lipid and lipoprotein levels in children in relation to their dietary habits and parental blood cholesterol]. / Hladiny sérových lipidu a lipoproteinu u detí ve vztahu k jejich nutricním návykum a k cholesterolémii rodicu.

In a group of 2000 Prague children aged 11-12 years the distribution of serum cholesterol levels was assessed. For further investigations 100 children with cholesterol levels above the 95th percentile (HYPER) were selected and 100 children with values between the 5th and 10th percentile (HYPO). Children and parents were subjected to detailed clinical and laboratory examination, in children the three-day dietary intake was assessed. Boys of the HYPER group had significantly higher LDL, HDL and VLDL cholesterol levels as well as levels of apolipoprotein B and less favourable values of the atherogenic index (AI). Girls of the HYPER group had significantly higher mean values of LDL-cholesterol and apolipoprotein B and also less favourable values of the AI. In the group HYPER children no abnormalities were detected in the carbohydrate metabolism nor a higher incidence of obesity although they differed significantly from children in the HYPO group as regards parameters of the lipid spectrum. The energy value of the consumed diet of children in the HYPER and HYPO group does not differ significantly. Although in boys of the HYPER group there was a higher ratio of total fat and animal fat (p less than 0.05), neither the percentage ratio of fatty acids nor the P:S ratio differed significantly in children of the HYPER and HYPO group. Parents of children of the HYPER group had significantly higher mean cholesterol, apolipoprotein B, LDL cholesterol values and less favourable values of the atherogenic index than parents of children of the HYPO group. The incidence of hypercholesterolaemia in the families of these children was also significantly higher.

Cholesterolaemia in school-age children and hypercholesterolaemia aggregation in the family.

The distribution of cholesterol values was established in a group of 2,000 Prague children aged 11-12 years. Of these, 100 children with cholesterol values exceeding the 95th percentile (HYPER), and 100 children with values between the 5th and the 10th percentiles (HYPO) were selected for follow-up. In addition to a thorough clinical and laboratory examination in children and parents, three-day food consumption was registered in children. Even though differing significantly from those assigned to the HYPO group in lipid spectrum parameters, HYPER group children did not show any abnormalities in carbohydrate metabolism or increased incidence of obesity. There is no significant difference in the energy values of food consumed by HYPER and HYPO children. Although a significantly higher proportion (in per cent) of total lipids and animal fat consumption was found in HYPER boys (p less than 0.05), the proportions (in per cent) of fatty acids, and the unsaturated/saturated fatty acid ratio in HYPER and HYPO children did no differ significantly. Parents of HYPER children showed significantly higher mean values of cholesterol, apolipoprotein B, LDL cholesterol and more unfavourable atherogenic index values. Hypercholesterolaemia aggregation in both parents was likewise significantly higher in children assigned to the HYPER group.

Distribution of blood pressure in children and adolescents.

Casual blood pressures were evaluated in 13 475 children and adolescents of elementary and secondary schools in the district of Prague 4. Measurements in an unselected children population determined mean systolic and diastolic pressures and standard deviations in different age groups. Children with elevated blood pressure were selected according to arbitrarily chosen criteria. Blood pressure greater than or equal to 130/80 mmHg (17.3/10.6 kPa) occurred in 0.6% of children aged 6-10 years, greater than 135/80 mmHg (17.9/10 kPa) in 2.0% of children aged between 11-15 years, and greater than 145/85 mmHg (19.2/11.3 kPa) in 0.4% of adolescents under 19 years.

Education and the risk factors of ischaemic heart disease.

Screening for the risk factors of ischaemic heart disease among the male residents of the district of Prague 4 aged 40--49 years was undertaken under the "National multifactorial primary preventive study of myocardial infarction and stroke". Of the 11 091 men invited, 5395 met the defined criteria and were admitted to the study. 58% of them were included in the risk group. The level of attained school education was ascertained at the initial examination. The lowest percentage of persons with hypercholesterolaemia, overweight, elevated blood pressure and smokers was found among university graduates. The results are compared with data of other studies and possible causes of the findings are discussed.

Prevalence of hypertension in children and adolescents.

The children in the population of the district of Prague 4 were screened for the prevalence of hypertension. From the age group 6--11 years (1st--5th forms), a representative sample was selected, comprising 2 152 children; of the age group 12--19 years (6th--9th forms and adolescents), 90% of the population (11 323 individuals) were examined. The arbitrarily set criteria of hypertension 130/80 mmHg in the children aged 6--11 years and 135/80 mmHg in those aged 12--19 years, were found acceptable for identification of potential hypertonics. In the population examined, such or higher pressures were found in 0.5--3.4% of the subjects examined. By thorough clinical and laboratory examinations of children aged 11--15 years with elevated blood pressures the participation of secondary hypertension was determined. In comparison with a control group, these children exhibited statistically significantly more frequent diseases, obesity, and faulty regimen of living, as well as hypertension in their parents.