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F Cambien

Publications and source records attributed to F Cambien.

At least 145 records · Page 8Linked to original sources
PubMed1991

Testing for association between disease and linked marker loci: a log-linear-model analysis.

One approach frequently used for identifying genetic factors involved in the process of a complex disease is the comparison of patients and controls for a number of genetic markers near a candidate gene. The analysis of such association studies raises some specific problems because of the fact that genotypic and not gametic data are generally available. We present a log-linear-model analysis providing a valid method for analyzing such studies. When studying the association of disease with one marker locus, the log-linear model allows one to test for the difference between allelic frequencies among affected and unaffected individuals, Hardy-Weinberg (H-W) equilibrium in both groups, and interaction between the association of alleles at the marker locus and disease. This interaction provides information about the dominance of the disease susceptibility locus, with dominance defined using the epidemiological notion of odds ratio. The degree of dominance measured at the marker locus depends on the strength of linkage disequilibrium between the marker locus and the disease locus. When studying the association of disease with several linked markers, the model becomes rapidly complex and uninterpretable unless it is assumed that affected and unaffected populations are in H-W equilibrium at each locus. This hypothesis must be tested before going ahead in the analysis. If it is not rejected, the log-linear model offers a stepwise method of identification of the parameters causing the difference between populations. This model can be extended to any number of loci, alleles, or populations.

Alleles↗
PubMed1990

Familial resemblance of plasma apolipoprotein B: the Nancy study.

The familial resemblance of plasma apolipoprotein B (apo B) was investigated in a sample of 102 families including 419 members who volunteered for a free health checkup in the Preventive Center of Vandoeuvre-lès-Nancy, France. The mean levels (+/- SD) of apo B were 141.0 (+/- 32.6), 121.8 (+/- 27.7), and 98.6 (+/- 22.6) mg/dl in fathers, mothers, and offspring, respectively. The familial correlations were 0.04, 0.13, 0.21 (P less than .01), and 0.47 (P less than .001) between spouses, father-offspring, mother-offspring, and siblings, respectively, after adjustment on age, body mass index, and sex. A genetic analysis was performed using the approach proposed by Bonney, which indicated that a recessive and a dominant major-locus model appeared nearly equally supported by the data. Under the recessive model, the frequency q of the most common allele was estimated as 0.825, with a mean difference of 60.4 mg/dl between high and low homozygotes. Under the dominant model, q was estimated as 0.875, with a mean increase of 34.2 mg/dl in heterozygotes and high homozygotes. However, the hypothesis of Mendelian transmission and the environmental hypothesis could not be formally tested because of great numeric difficulties encountered in the estimation of the three transmission probabilities. Given these analytical restrictions, we cannot conclude in favor of a major locus influencing apo B level in our population, even though the evidence is suggestive. The genetic heterogeneity underlying the familial aggregation of apo B level, suggested by several recent publications, might explain the difficulty in discerning a single major locus in a population sample of small nuclear families, not ascertained through patients enriching the sample in high values of apo B. These findings call into question the relevance of the approach through "healthy" populations in the search for major loci influencing biological traits.

Adult↗
PubMed1990

Detection by denaturing gradient gel electrophoresis of a new polymorphism in the apolipoprotein B gene.

The apolipoprotein B gene is subject to mutations that may be important in coronary heart diseases. We have used polymerase chain reaction and denaturing gradient gel electrophoresis to characterize a single nucleotide substitution in the apolipoprotein B gene. This mutation affects amino acid 4311 of the protein and converts asparagine to serine. It was found in 24% of the 81 unrelated individuals analyzed. Moreover, another mutation was detected by sequencing in a single individual.

Apolipoproteins B↗
PubMed1990

Similar frequencies of renin gene restriction fragment length polymorphisms in hypertensive and normotensive subjects.

A prospective study was conducted to compare the frequency of renin gene polymorphisms in normotensive and hypertensive subjects. Hypertensive (n = 102, blood pressure 168 +/- 17/103 +/- 9 mm Hg) and normotensive (n = 120, blood pressure 122 +/- 10/75 +/- 9 mm Hg) subjects were white, had similar age and sex distributions (hypertensive group, 45 +/- 10 years old and 52% female; normotensive group, 44 +/- 9 years old and 55% female) and similar body mass index (hypertensive group, 23.2 +/- 2.6; normotensive group, 22.5 +/- 2.4 kg/m2, p = 0.048). The familial susceptibility to hypertension was defined as at least one parent and one sibling who were hypertensive before age 65; subjects in the normotensive group had no familial history of hypertension. Renin gene polymorphisms located throughout the renin gene were identified by using three restriction enzymes (Taq I, HinfI, HindIII). For each polymorphic restriction site, allele frequencies were similar in the hypertensive and the normotensive groups. In the absence of parental genotypes, the haplotype frequencies combining the three restriction fragment length polymorphisms were estimated by using maximum likelihood techniques and were similar in both groups (hypertensive group, 0.429, 0.277, and 0.177; normotensive group, 0.453, 0.245, and 0.195 for the three most common haplotypes). A rare haplotype detected by Taq I/Hind III was apparently more frequent in the hypertensive than in the normotensive group (hypertensive group, tH 0.086, th 0.022; normotensive group, tH 0.038, th 0.050), but the difference was not statistically significant. In conclusion, no association between renin gene polymorphisms and essential hypertension was demonstrated in the present study.

Adult↗
PubMed1990

An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels.

A polymorphism consisting of the presence or absence of a 250-bp DNA fragment was detected within the angiotensin I-converting enzyme gene (ACE) using the endothelial ACE cDNA probe. This polymorphism was used as a marker genotype in a study involving 80 healthy subjects, whose serum ACE levels were concomitantly measured. Allele frequencies were 0.6 for the shorter allele and 0.4 for the longer allele. A marked difference in serum ACE levels was observed between subjects in each of the three ACE genotype classes. Serum immunoreactive ACE concentrations were, respectively, 299.3 +/- 49, 392.6 +/- 66.8, and 494.1 +/- 88.3 micrograms/liter, for homozygotes with the longer allele (n = 14), and heterozygotes (n = 37) and homozygotes (n = 29) with the shorter allele. The insertion/deletion polymorphism accounted for 47% of the total phenotypic variance of serum ACE, showing that the ACE gene locus is the major locus that determines serum ACE concentration. Concomitant determination of the ACE genotype will improve discrimination between normal and abnormal serum ACE values by allowing comparison with a more appropriate reference interval.

Adult↗
PubMed1990

[Up-date on atherosclerosis].

The major steps of the pathogenesis of atherosclerosis are now well defined. Efforts are still required to better characterize: 1. the cellular mechanisms of atherogenesis, without ignoring the limitations of the available experimental models; 2. the complications of human atherosclerosis, ie the events (ulceration, thrombosis) that provoke ischaemic manifestations. Four short reviews on topics of special interest follow: proliferation of arterial smooth muscle cells; interactions of blood cells (platelets, leukocytes) with the arterial wall; lipoproteins in the genesis of foam cells; recent progresses in genetic epidemiology of cardiovascular diseases.

Animals↗
PubMed1989

Hypertriglyceridaemia as a risk factor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes. Results from the 11-year follow-up of the Paris Prospective Study.

The Paris Prospective Study is a long-term investigation of the incidence of coronary heart disease in a large population of working men. The first follow-up examination involved 7,038 men, aged 43-54 years. Subjects with impaired glucose tolerance or diabetes (n = 943) were selected from the total population for a separate analysis of coronary heart disease mortality risk factors. During a mean follow-up of 11 years, 26 of these 943 subjects with abnormal glucose tolerance died from coronary heart disease. Univariate analysis showed that plasma triglyceride level (p less than 0.006), plasma cholesterol level (p less than 0.02), and plasma insulin level both fasting and 2-h post-glucose load (p less than 0.02), were significantly higher in subjects who died from coronary heart disease compared to those who did not. In multivariate regression analysis using the Cox model, plasma triglyceride level was the only factor positively and significantly associated with coronary death. The distribution of plasma triglyceride levels was clearly higher for the subjects who died from coronary heart disease compared to those who did not die from this cause or were alive at the end of the follow-up. This new epidemiological evidence that hypertriglyceridaemia is an important predictor of coronary heart disease mortality in subjects with impaired glucose tolerance or diabetes suggests a possible role of dyslipidaemia in the excessive occurrence of atherosclerotic vascular disease in this category of subjects.

Blood Glucose↗
PubMed1989

Pulsatile versus steady component of blood pressure: a cross-sectional analysis and a prospective analysis on cardiovascular mortality.

Studies on the prognostic significance of blood pressure on cardiovascular disease have essentially investigated the levels of diastolic or systolic blood pressure. However, blood pressure may also be divided into two other components: steady (mean arterial pressure) and pulsatile (pulse arterial pressure). The relations of these two components with cardiovascular risk factors and cardiovascular mortality were investigated in 18,336 men and 9,351 women aged 40-69 years, who were followed up for a mean period of 9.5 years. However, the interpretation of the relations is complicated by the strong correlation existing between these two components. A principal component analysis was performed to obtain two independent parameters: a steady and a pulsatile component index, strongly correlated with mean and pulse arterial pressure, respectively. In the cross-sectional analysis, relations were stronger with the steady component index than with the pulsatile component index; an association was found between left ventricular hypertrophy and the pulsatile component index in both sexes. The survival analysis was not performed in women under 55 as only 11 cardiovascular deaths occurred in this group. The steady component index was a strong prognostic factor of all types of cardiovascular death in both sexes. In women, the pulsatile component index was positively correlated to death from coronary artery disease and inversely correlated to stroke. In conclusion, the steady component of blood pressure is a strong risk factor for cardiovascular death in both sexes; the pulsatile component could be a risk factor independent of the steady component in women older than 55 years.

Adult↗
PubMed1989

The application of molecular genetics to the study of familial arterial hypertension.

The hereditary nature of familial hypertension has been clearly established by a number of clinical studies. Most of the present work has been concentrated on the correlation between various phenotypic traits and the level of blood pressure. The development of molecular genetics allow now to establish a link between high blood pressure and specific phenotypes. As analyzed in this paper, several strategies can be used for the genetic study of arterial hypertension: linkage studies in informative families, population association studies, analysis of subjects with contrasted predisposition to high blood pressure, affected sib-pair method. The identification of the loci implicated in blood pressure regulation and which contribute to the development of arterial hypertension can then be performed in this clinical material by two main approaches. One is based on the study of candidate genes, genes whose products are known to participate in blood pressure regulation, such as those of the renin-angiotensin system which are examplified. The other involves testing a series of markers distributed randomly throughout the genome in order to establish a link between increased blood pressure and a particular region of the genome.

Female↗
PubMed1988

Combined effects of gender and hypertension on the geometric design of large arteries. Sexual differences in normal and hypertensive forearm arteries.

The effects of sex, hypertension, morphologic status, and heart rate were assessed on the large arteries of 46 normotensive subjects (23 men and 23 women) and 50 hypertensive patients (25 men and 25 women) by means of pulsed Doppler determination of diameter and blood velocity of the brachial artery. Compared to men, women had lower height, weight, and forearm volume (P less than 0.001), higher heart rate (P less than 0.001), and lower brachial artery diameter (P less than 0.001) both in the normotensive and hypertensive groups. Compared to normotensives, hypertensives of the same sex showed an increase in brachial artery diameter, only significant in men (P less than 0.001), and an increase in heart rate, only significant in women (P less than 0.001). The multiple regression analysis of brachial artery diameter showed significant coefficients for sex and hypertension (P less than 0.001), and for age and heart rate (P less than 0.05); the multiple regression analysis of blood velocity showed that only the coefficient of hypertension was significant (P less than 0.05). The study of first-order interactions between the independent variables revealed that effect of sex on arterial diameter did not depend on the other variables. In contrast the effects of age and heart rate were influenced by the presence or the absence of hypertension, and arterial caliber was positively related to age in normotensive subjects (P less than 0.05) but not in hypertensive patients, and negatively related to heart rate in hypertensive patients (P less than 0.001) but not in normotensive subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

An epidemiologic appraisal of the associations between the fatty acids esterifying serum cholesterol and some cardiovascular risk factors in middle-aged men.

The relations between the fatty acids of cholesterol esters and some cardiovascular risk factors have been investigated in a sample of 3,348 middle-aged men examined at entry into the Paris Prospective Study 2. The partial associations between the risk factors and the various fatty acids have been evaluated using a special regression method that takes into account the structural dependencies among the percentages of fatty acids. The results show that palmitoleic acid is strongly associated with alcohol consumption and blood pressure and that its association with blood pressure is absent in nondrinkers. High density lipoprotein cholesterol and apolipoprotein A1 are negatively associated with palmitic and dihomogammalinolenic acids and positively associated with oleic and linoleic acids. An inverse relation of low density lipoprotein cholesterol and apolipoprotein B to these fatty acids is also observed. Simultaneous high levels of palmitic and dihomogammalinolenic acids and low levels of oleic and linoleic acids could then be related to profiles of lipids and apolipoproteins exposing one to a high risk of coronary heart disease. These associations may be of interest in interpreting the relations observed in other studies between the fatty acid composition of cholesterol esters or other lipids and coronary heart disease.

Blood Pressure↗
PubMed1988

Familial resemblance of plasma angiotensin-converting enzyme level: the Nancy Study.

Plasma angiotensin I-converting enzyme (ACE) activity has been measured in a sample of 87 healthy families participating in a study of cardiovascular risk factors. The mean +/- SD levels of plasma ACE were 34.1 +/- 10.7, 30.7 +/- 10.4 and 43.1 +/- 17.2 units/liter in fathers (n = 87), mothers (n = 87) and offspring (n = 169), respectively. Plasma ACE was uncorrelated with age, height, weight, or blood pressure in the parents, but a negative correlation with age was observed in offspring (r = -.32). The age-adjusted familial correlations of plasma ACE were .038, .166, .323 and .303 for spouses, father-offspring, mother-offspring, and siblings, respectively. The results of the genetic analysis suggest that a major gene may affect the interindividual variability of plasma ACE, with different codominant effects in parents and offspring. According to this model, the major gene effect accounts for 4.8, 4.0, and 10.8 units/liter of the overall mean and for 29%, 29% and 75% of the variance of age-adjusted ACE in fathers, mothers, and offspring, respectively. The estimate of the probability of the less frequent allele is .26, and the major gene effect is approximately twice as great in high homozygotes than in heterozygotes and in offspring than in parents. The results of this study demonstrate the occurrence of a familial resemblance of plasma ACE activity in healthy families and suggest that this observation can be explained by the segregation of a major gene.

Alleles↗
PubMed1988

[Relationship between blood pressure level and different types of alcoholic beverages].

The relationship between alcohol consumption (AC) has been repeatedly confirmed. However, the respective contribution of the various types of beverages has not been clearly established. The cross-sectional data of the initial examination of the Paris prospective study II of the GREA, concerning 4547 male civil servants were thus analysed. Among subjects without any antihypertensive medication, systolic (SBP) and diastolic (DBP) blood pressure were positively associated with total AC; the differences between the first and the fifth quintile were respectively 6 and 3 mmHg (p less than 0.01 for wine, beer and spirits consumption). Using a linear combination of wine, beer and spirits consumption significantly improved the prediction of BP, as compared to total AC (p less than 0.001). In the multivariate analysis including age and body mass index (BMI), the consumption of 40 ml of alcohol from beer was associated with an increase of 5.7 mmHg for SBP and 2.6 mmHg for DBP (p less than 0.001). The elevation was 2.3 (SBP, p less than 0.001) and 0.8 mmHg (DBP, p less than 0.01) for wine consumption. Spirits consumption was associated with DBP (1.4 mmHg, p less than 0.001), but not with SBP. In conclusion, a positive relationship was observed with each of the three types of alcoholic beverages studied; however, this association was more pronounced for beer than for the two other beverages.

Adult↗
PubMed1987

Relation of parental history of early myocardial infarction to the level of apoprotein B in men.

The relations between parental history of early myocardial infarction and plasma lipids and apoproteins have been examined in a population of 4045 middle-aged (20 to 60 years old) working men at the initial examination of the Paris Prospective Study 2. Subjects with a history of myocardial infarction, angina pectoris, or peripheral arterial disease or those treated with hypolipidemic drugs were excluded from the analysis. The numbers of subjects with a paternal or maternal history of early myocardial infarction were 123 and 30, respectively. After adjustment for age, cigarette consumption, alcohol consumption, and body mass index, subjects with parental history of myocardial infarction had higher levels of total cholesterol (p less than .01), low-density lipoprotein (LDL) cholesterol (p less than .01), and apoprotein B (APOB) (p less than .0001) and a lower level of high-density lipoprotein (HDL) cholesterol (p less than .05) than subjects with no parental history of myocardial infarction. On the other hand, apoprotein A1 (APOA1) and triglyceride levels were not different between the two groups. The ratios of HDL/total cholesterol and APOA1/APOB were also lower in presence of parental myocardial infarction (p less than .001 and p less than .01, respectively). When a discriminant analysis was performed, only APOB level was related to parental myocardial infarction. The results for paternal and maternal history were very similar and were grouped for the analysis. We conclude that part of the known relationship between parental history of myocardial infarction and coronary heart disease could be mediated by an increased APOB level.

Adult↗
PubMed1987

[Effect of smoking on blood viscosity and arterial rigidity in normal and hypertensive subjects].

The purpose of the study was to assess whether cigarettes smoking could induce blood hyperviscosity and arterial rigidity in 30 normotensive and 70 hypertensive men aged from 24 to 65 years. Of those, 20 normotensive and 20 hypertensive were cigarettes smokers, while the remaining subjects were non smokers. Age and weight were similar in the 4 groups of subjects. A couette viscometer with coaxial cylinders allowed the measurements of blood viscosity over a wide range of shear rates (0.033 to 241 sec-1) mimicking the flow condition of the circulation, and two strain gauge transducers permitted the measurements of the brachial to radial pulse wave velocity as an index of arterial wall distensibility. In normotensive subjects cigarettes smoking increased pulse wave velocity from 7.1 + 1 to 9.2 + 0.6 m/sec. (P less than 0.05) as well as blood viscosity, which increased both at higher shear rates (+10% from 52 to 241 sec-1, P less than 0.05) and lower shear rates (+20% from 11.2 to 0.2 sec-1, P less than 0.02). In hypertensives, cigarettes smoking increased pulse wave velocity (9.8 + 0.3 to 11.3 + 0.4; P less than 0.05) and blood viscosity (4% at higher shear rate P less than 0.05 and 10% at lower shear rates P less than 0.02). Although hypertensive patients had increased pulse wave velocity and blood viscosity compared to normotensive controls, these variables were not significantly different when hypertensive non smokers were compared to normotensive. The present study demonstrated that cigarettes smoking produced in normotensive and hypertensive men significant rheological disturbances of flow and wall arteries.2

Adult↗
PubMed1987

Is insulin the key factor to explain the associations between body mass, blood pressure and glucose?

The relationships between body mass index (BMI), fasting plasma glucose and insulin and blood pressure level have been investigated in a group of 2,144 healthy middle-aged men. The associations between BMI and blood pressure are largely independent of plasma glucose and insulin. Plasma glucose is strongly related to blood pressure in non-obese subjects. Plasma insulin is not associated with blood pressure independently of BMI and plasma glucose, although the simultaneous elevation of BMI, plasma glucose and insulin is strongly associated with blood pressure.

Adult↗