Biomedical subjects
F Angelico
Publications and source records attributed to F Angelico.
[Plasma fibrinogen and cardiovascular risk factors. The experience of the Integrated Community Control Project on Chronic Degenerative Diseases in the Health District of Sezze--Di.S.Co. The Research Group].
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Role of genetic variation at the apo AI-CIII-AIV gene cluster in determining plasma apo AI levels in boys and girls.
We have investigated the effect of the G/A substitution in the promoter region of the apolipoprotein (apo) AI gene (-75 bp) on plasma lipid, lipoprotein and apolipoprotein levels in a sample of 204 children from central Italy. The subjects included 111 boys and 93 girls, aged 8-11 years old. The frequency of the A allele was 0.19 in the total sample, and 0.21 and 0.17 in boys and girls, respectively. Using analysis of variance, we found the G/A substitution was significantly associated with plasma levels of total cholesterol, LDL cholesterol, apo B, and apo AI in boys, accounting for 7.0, 4.2, 5.3, and 4.3% of the sample variance, respectively. Individuals with an A allele had higher mean levels of these lipid traits than individuals homozygous for the G allele. A dietary intervention study had been carried out in a subset of these children, and the effect of the G/A substitution on plasma apo AI levels remained when boys changed to a low fat low cholesterol diet. However, no significant association was observed in girls between any of the lipid traits and the G/A genotypes. We have previously reported in this sample of children that the two polymorphisms detected with restriction enzyme PvuII, with variable sites in the first intron of the apo CIII gene (Pvu II-CIII) and the apo CIII-AIV intergenic region (Pvu II-AIV), were associated with significant differences on plasma apo AI levels. We found that the association reached statistical significance in boys only in this study. Taking these three polymorphisms together, the effects on plasma apo AI levels were additive in boys, accounting for 20.0% of the sample variance. Boys having the genotype GG/V-V+ of the G/A substitution and the PvuII-AIV RFLP had mean apo AI levels 36 mg/dl lower than boys with the genotype GA + AA/V-V-. In girls, however, there was evidence of significant interaction of effects between the PvuII-AIV RFLP and the G/A substitution (P < 0.04), with the A allele being associated with higher levels of plasma apo AI only in girls having the rare allele (V+) of the PvuII-AIV RFLP. We conclude that genetic variation at the apo AI-CIII-AIV gene cluster is having a major impact on the determination of plasma apo AI levels in this sample of young boys, with additive effects due to functional changes at several places in this gene cluster detected directly (G/A) or in allelic association with the PvuII-CIII and PvuII-AIV polymorphisms.(ABSTRACT TRUNCATED AT 400 WORDS)
[Reliability and power of genetic studies].
During the last few years new powerful diagnostic methods have been developed in the field of molecular and cell biology. It is now possible to work out the molecular pathology of many genetic diseases and to institute new techniques for the detection of carriers and neonatal diagnosis. However, it is in the field of polygenic diseases such as degenerative vascular disease, diabetes, cancer and other chronic diseases that molecular biology will play its most important part and perhaps change in the long term our clinical approach. There is considerable debate among geneticists on the safest strategy for obtaining and long term storing sufficient DNA from an individual for projects requiring large but unknown amounts of DNA. As little as 0.5 ml whole, blood samples (or white cells) which have been frozen with 10% DMSO or anticoagulants will provide sufficient DNA by direct extraction methods and also permit to establish lymphoblastoid cell lines providing an infinite source of DNA.
Apolipoprotein E polymorphism and plasma lipid, lipoprotein, and apolipoprotein levels in Italian children.
We have investigated the effect of apolipoprotein (apo) E polymorphism on serum lipid, lipoprotein, and apolipoprotein levels in a sample of 195 children, aged 8-11 years, from Sezze, Central Italy. The relative frequencies of e2, e3, and e4 alleles were 0.062, 0.867, and 0.072, respectively. Variation at the apo E gene locus explained 5.1% of the sample variance in serum total cholesterol levels, 7.6% in low-density lipoprotein (LDL) cholesterol levels, 7.3% in apo B levels, and 14.1% in high-density lipoprotein-apo E (HDL-E) levels. The effect of the e2 allele was to lower levels of total cholesterol, LDL-cholesterol, and apo B and to raise levels of HDL-E, while the effect of the e4 allele was the opposite. Variation at the apo E gene locus was not associated with differences in serum triglyceride, HDL-cholesterol, or apo AI levels. The effects of common apo E polymorphisms and genetic variation associated with the PvuII RFLP of the apo B gene on serum apo B levels were additive, explaining 11.3% of the phenotypic variance in this sample. When the effect of apo E polymorphism on serum lipid traits was estimated in boys and girls separately, variation at the apo E gene locus explained 10.4, 13.3, 13.3, and 13.5% of the phenotypic variance in serum total cholesterol, LDL-cholesterol, apo B, and HDL-E levels, respectively, in boys, while in girls only the effect on HDL-E levels (19.3%) reached statistical significance. This study has demonstrated that genetic variations at the apo E locus contribute to the determination of serum lipid, lipoprotein, and apolipoprotein levels in youths and that the effects are gender specific.
Management of childhood obesity through a school-based programme of general health and nutrition education.
A school-based nutrition education programme aimed at the control of coronary risk factor rise during childhood was started in 1983 for 150 boys and girls aged 6-7 years. The study was performed in a rural area of central Italy, where adult obesity represents a major health problem. Preventive treatment was based on general health education in schools towards healthy lifestyles. Nutritional intervention was mainly focused on the adoption of the 'prudent diet'. School-teachers received specific training on how to teach 'good nutrition'. The nutrition curriculum was taught by teachers throughout the school year. Several meetings were organised to actively involve the children's parents. Practical recommendations for changes in food selection and preparation were also given. After a five-year follow up, a strong 'tracking phenomenon' for body mass index was observed, suggesting a great stability over time of lifestyles and dietary habits leading to the development of obesity during childhood. We conclude that a school-delivered programme of general nutrition education for the control of risk factors does not appear to be able to control child obesity.
INTERSALT in Italy: findings and community health implications.
In INTERSALT, an international cooperative study on electrolytes and blood pressure, significant associations were found, in the pooled data for 52 centres, between systolic BP and sodium (Na) excretion, body mass index (BMI), high alcohol intake and low potassium (K) excretion. We have assessed the status of the four Italian centres (Mirano, Gubbio, Bassiano, Naples) on these variables. The four centres examined a total of 794 men and women aged 20-59 years. Combined values were similar to overall INTERSALT levels for daily Na excretion (170 mmol) and BMI (25 kg/m2). The Italian centres had slightly higher potassium excretions (57 vs. 55 mmol/day), a higher prevalence of drinkers and a greater average alcohol consumption. Participants were divided into those below or above median levels of Na, K, BMI, and by alcohol intake (below or above 300 ml/week). Both systolic BP and diastolic BP were found to be lower in the more favourable stratum, for each variable. When all four factors were combined, those below median Na excretion and BMI, above median K, and with alcohol intake less than 300 ml/week had age-adjusted systolic BP 7.5 mmHg lower than those with less favourable levels of all four variables. The difference in adjusted diastolic BP was 4.3 mmHg. The data indicate the potential for lower population average BP with improved lifestyles.
High prevalence of obesity in a rural community of central Italy: the 'Di.S.Co.' Project.
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Strong association of overweight to high blood pressure in a rural community of central Italy: the 'Di.S.Co.' Project.
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Variation at the apolipoprotein (apo) AI-CIII-AIV gene cluster and apo B gene loci is associated with lipoprotein and apolipoprotein levels in Italian children.
We have used RFLPs of the apolipoprotein (apo) B gene and apo AI-CIII-AIV gene cluster to estimate the genetic contribution of variation at these loci to the variability of plasmid lipid, lipoprotein, and apolipoprotein levels in 209 children from Sezze in central Italy. The sample was randomly divided into group I (107 children) and group II (102 children). Four site polymorphisms (PvuII, XbaI, MspI, and EcoRI) of the apo B gene and five site polymorphisms (XmnI, PstI, SstI, PvuII-CIII, and PvuII-AIV) of the apo AI-CIII-AIV gene cluster were examined in group I children. After adjustment for gender, age, and body-mass index, polymorphisms at both gene loci (PvuII-B, PvuII-CIII, and PvuII-AIV) were associated with significant effects on the levels of plasma apo AI, apo B, or high-density lipoprotein-cholesterol. RFLPs that showed significant effects in group I were genotyped in group II. All three polymorphisms were associated with similar effects on apolipoprotein levels, though for all RFLPs the magnitude of the effects was smaller in the group II children and only statistically significant for the effect of the PvuII-B genotype on apo AI levels. In the total sample of 209 children 7.4% of the sample variance in apo AI levels was explained by variation associated with the apo B PvuII-B RFLP. In addition, the PvuII-B RFLP was associated with significant effects on plasma apo B levels and explained 5.7% of the sample variance. The PvuII-CIII and PvuII-AIV polymorphisms were both associated with differences in apo AI levels, explaining 3.7%-5.7% of the sample variance. Taken together, the three PvuII polymorphisms explained 17.7% of the phenotypic variance in apo AI levels. There was significant evidence for an effect of nonlinearity of the PvuII-CIII genotypes on apo AI levels, with the individuals heterozygous for the polymorphism having the highest apo AI levels. No evidence of interaction between genotype and gender, age, and body-mass index was shown by covariance analysis. The molecular explanation of this effect is unclear. Our data show that variation at both the apo AI-CIII-AIV and apo B loci are associated with lipoprotein and apolipoprotein levels in this sample of Italian children.
Apolipoprotein B amino acid 3611 substitution from arginine to glutamine creates the Ag (h/i) epitope: the polymorphism is not associated with differences in serum cholesterol and apolipoprotein B levels.
A G- to A-DNA sequence change in exon 26 of the human apolipoprotein B (apo B) gene leads to a glutamine substitution for arginine at codon 3611 of the mature apolipo-protein B100 and causes a loss of an MspI site. In 106 Finnish individuals, a complete correspondence exists between this MspI polymorphic site and the Ag (h/i) immunochemical polymorphism. Linkage disequilibrium was found between this MspI polymorphic site and the apo B XbaI and EcoRI variable sites and the Ag (al/d) and (c/g) epitope pairs; there is apparent linkage equilibrium with the apo B PvuII variable site. Based on three population studies (samples from London. Finland and Italy), no significant association was found between this RFLP and serum cholesterol and apo B levels. These data suggest that the arginine 3611----glutamine 3611 substitution has no significant effect on apo B function.
Erythrocyte fatty acid composition and gallstone disease: results of an epidemiological survey.
Within a cross-sectional study on the epidemiology of gallstone disease (GD) and its related factors, relation of GD to habitual dietary fat types has been investigated. Gallbladder status was assessed by ultrasound; fatty acid composition of the habitual diet was estimated by GLC of erythrocyte fatty acids. No differences in erythrocyte fatty acid composition were observed between women without gallstones, women with gallstones (aware and unaware of their condition), and women who had cholecystectomies. Multivariate analysis, including other diet-dependent and gallstone-related variables, showed no significant association between erythrocyte fatty acids and risk for gallstones. However, raised erythrocyte linoleic:saturated ratio was associated with increased risk for gallstones only in women with very low serum triglycerides. This latter finding needs further confirmation and is presently unexplainable. Our results suggest that dietary fatty acids do not play a major role in GD.
Use of diethylaminoethyl-dextran (DEAE-D) in the treatment of hyperlipoproteinemias and obesity.
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Lack of association between arterial blood pressure and erythrocyte fatty acid composition in an Italian population sample.
The relation between arterial blood pressure and erythrocyte fatty acid composition was investigated in a large urban female population aged 20-69 years. No significant differences in the relative amounts of saturated, monounsaturated and polyunsaturated (n-6 and n-3 series) fatty acids and in the mean polyunsaturated/saturated and linoleic/oleic ratios were observed in the different quartiles of both systolic and diastolic blood pressure. Moreover, there was no significant correlation between individual erythrocyte fatty acids and their ratios and either blood pressure or other risk factors for atherosclerosis (age, body mass index, total serum cholesterol and triglycerides). In the multivariate analysis no independent correlations between systolic and diastolic blood pressure and the individual erythrocyte fatty acids were observed; age and body mass index were strongly related to blood pressure. Our results do not confirm for erythrocyte fatty acids the reported associations between plasma fatty acids and blood pressure.
[Effects of the integration of a habitual diet with glucomannan fiber in hypercholesterolemia. A clinical study in familial and sporadic hyperlipoproteinemia with lipo-proteic phenotype IIa and IIb].
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Plasma lipid lipoproteins and biliary lipid composition in female gallstone patients.
The relationships between biliary lipid composition and cholesterol or triglyceride concentration in plasma lipoprotein fractions (i.e., very-low density, low-density, high-density, HDL2 and HDL3) have been studied in normolipaemic female gallstone patients. Univariate and multivariate stepwise statistical analyses were used to correlate biliary-tested variables against lipid lipoprotein concentration. Cholesterol saturation index was found to be positively and independently associated with total triglycerides, very-low-density lipoprotein triglycerides, very-low-density lipoprotein cholesterol and furthermore, negatively, with HDL3-cholesterol. Percent biliary deoxycholate was positively correlated with both cholesterol saturation index and plasma very-low-density cholesterol or triglycerides. Neither cholesterol saturation index nor percent biliary deoxycholate showed any correlation with total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, HDL2-cholesterol. The present findings suggest a linkage between biliary deoxycholate, biliary cholesterol saturation and plasma very-low-density lipoprotein levels in gallstone patients. Furthermore, since the lipoprotein risk factors for coronary heart disease showed no correlation with cholesterol saturation index, these results were considered a biochemical proof against the supposed association between coronary heart disease and gallstone disease.
Plasma cholesterol response to a change in dietary fat intake: a collaborative twin study.
The rise of plasma cholesterol in response to an increase from 8 to 22.3% in saturated fatty acid of total intake was studied by comparing the concordance of change in pairs of young English and Italian monozygotic (33 pairs) and dizygotic (22 pairs) twins. LDL and total cholesterol rose about 0.6 mmol/l. All methods of analyses showed a marked genetic component influencing total and LDL cholesterol level. However, the genetic component of the increase in LDL and total cholesterol levels was small in Italy and absent in England. These results suggest that the response of plasma cholesterol to this dietary change is largely determined by environmental factors rather than inheritance.
Plasma and erythrocyte fatty acids: a methodology for evaluation of hypocholesterolemic dietary interventions.
A major source of concern in the management of hypercholesterolemia is the careful evaluation of adherence to dietary prescriptions. Routine analysis of plasma fatty acids to monitor adherence of hyperlipidemic outpatients to diets varied in lipid composition is a major task of our research group. Plasma fatty acid patterns are determined by gas-liquid chromatography 60 days after starting an experimental normocaloric diet with 37% fat calories and a polyunsaturated/saturated (P/S) ratio of 3.4. Where poor adherence is observed, the dietary message is administered more incisively or changed accordingly. It is also possible to identify with certainty diet-resistant hypercholesterolemic individuals, i.e., the true nonresponders, who represent only a minority. The determination of erythrocyte fatty acid patterns represents a useful index of adherence in long-term feeding studies and has been extensively carried out in subsamples of persons examined at the fourth rescreening of a controlled trial of primary prevention of coronary heart disease. Increases in mean erythrocyte linoleic/oleic (L/O) and P/S ratios were observed in persons undergoing collective or individual hypocholesterolemic treatment, mean changes being proportional to the different type of nutritional approach. In our opinion, this methodology is the most reliable technique not only for the identification of the different responses to hypocholesterolemic dietary recommendations but also to monitor fat consumption in population samples.