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Biomedical subjects

F Cambien

Publications and source records attributed to F Cambien.

At least 127 records · Page 7Linked to original sources
PubMed1994

Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension.

We conducted the present study to determine whether the angiotensin II type I receptor (AT1) gene might be implicated in human essential hypertension by using case-control and linkage studies. The entire coding and 3' untranslated regions of the AT1 receptor gene (2.2 kb) were amplified by polymerase chain reaction and submitted to single-strand conformation polymorphism in 60 hypertensive subjects with a familial susceptibility. We identified five polymorphisms (T573-->C, A1062-->G, A1166-->C, G1517-->T, and A1878-->G). However, no mutations that alter the encoded amino acid sequence were detected. A case-control study performed on white hypertensive (n = 206; blood pressure, 168 +/- 16/103 +/- 9 mm Hg) and normotensive (n = 298; blood pressure, 122 +/- 10/75 +/- 9 mm Hg) subjects using three of five polymorphisms showed a significant increase in allelic frequency of C1166 in hypertensive subjects (0.36 versus 0.28 for normotensive subjects, chi 2 = 6.8, P < .01). Frequencies for the alleles of the other two polymorphisms (T573-->C, A1878-->G) were similar in both groups. We performed a linkage study using the affected sib pair method and a highly polymorphic marker of the AT1 receptor gene. There was no evidence for linkage in 267 sib pairs analyzed from 138 pedigrees. These findings would be compatible with a common variant of the AT1 receptor imparting a small effect on blood pressure; further studies will be needed to address this possibility.

Adult↗
PubMed1994

Relationships between angiotensin I converting enzyme gene polymorphism, plasma levels, and diabetic retinal and renal complications.

Insulin-dependent diabetes mellitus (IDDM), cardiovascular morbidity, and vital prognosis are linked to diabetic nephropathy, which is probably determined by renal hemodynamic abnormalities and by a genetic predisposition. Angiotensin I converting enzyme (ACE) regulates systemic and renal circulations through angiotensin II formation and kinins metabolism. Plasma and cellular ACE levels are genetically determined; an insertion/deletion polymorphism of the ACE gene is strongly associated with ACE levels, subjects homozygote for insertion (genotype II) having the lowest plasma values. We studied the relationship between the ACE gene polymorphism or plasma levels and microcirculatory disorders of IDDM through two independent studies: one involved 57 subjects with or without diabetic retinopathy, and the other compared 62 IDDM subjects with diabetic nephropathy to 62 diabetic control subjects with the same characteristics (including retinopathy severity) but with normal kidney function. The ACE genotype distribution was not different in diabetic subjects with or without retinopathy and in a healthy population. Conversely, an imbalance of ACE genotype distribution, with a low proportion of II subjects, was observed in IDDM subjects with diabetic nephropathy compared with their control subjects (P = 0.006). Plasma ACE levels were mildly elevated in all diabetic groups, independently of retinopathy, but they were higher in subjects with nephropathy than in those without nephropathy (P = 0.0022). The II genotype of ACE gene is a marker for reduced risk for diabetic nephropathy.

Adolescent↗
PubMed1994

Expression of a paternal history of premature myocardial infarction on fibrinogen, factor VIIC and PAI-1 in European offspring--the EARS study. European Atherosclerosis Research Study Group.

To assess the role of genetic and environmental factors in the predisposition to atherosclerosis, 682 students whose father had suffered a myocardial infarction before the age of 55 ("cases") and 1312 controls matched for age and sex, were recruited from 14 Universities in Europe. Fibrinogen, factor VIIc and PAI-1 were compared between cases and controls across European regions. Fibrinogen and factor VIIc were positively correlated with BMI, smoking and contraception. PAI-1 was positively and independently correlated with BMI and waist-to-hip ratio, and negatively with contraception. Factor VIIc and PAI-1 were correlated with cholesterol and triglycerides, and fibrinogen was weakly correlated with LDL-cholesterol. After adjustment for covariates and lipids, fibrinogen level was significantly higher in male cases than in controls (2.38 vs 2.29, p < 0.01). No such difference was found in females (2.59 vs 2.57 - NS). There was no significant case/control difference for factor VIIc and PAI-1. These results support the hypothesis that fibrinogen is a transmissible risk factor of coronary artery disease in males. No such evidence was provided for factor VIIc and PAI-1.

Adolescent↗
PubMed1994

Polymorphisms of the angiotensin-converting-enzyme gene in subjects who die from coronary heart disease.

It has been shown that myocardial infarction survivors are more likely to carry an insertion/deletion polymorphism (I/D) of the angiotensin-converting-enzyme (ACE) gene than age-matched population controls. To test whether the association with coronary risk had been under-estimated, the frequency of the ACE I/D was studied in 213 fatal cases of definite and possible myocardial infarction which came to autopsy in the Belfast MONICA Project area. In comparison to controls from the same population, the autopsy cases had an increased frequency of the ACE D allele (p < 0.02). The overall odds ratios were 2.2 for DD vs. II, and 1.8 for ID vs II (test for trend p = 0.01). The findings bear out the hypothesis that the ACE I/D polymorphism is a risk factor for fatal myocardial infarction and sudden cardiac death.

Adult↗
PubMed1993

Reliability of reported family history of myocardial infarction.

OBJECTIVE: To assess the reliability of reported family histories of myocardial infarction. DESIGN: A case-control study in which reported histories of first degree relatives were validated from death certificates, general practitioners' records, and hospital notes. SETTING: Participants enrolled in the Belfast centre of the World Health Organisation's study monitoring trends and determinants in cardiovascular disease (MONICA). SUBJECTS: 200 men who survived myocardial infarction and 200 age matched controls drawn randomly from the population. MAIN OUTCOME MEASURES: The sensitivity, specificity, positive predictive value, and proportion of overall agreement with validated records of reported family histories of myocardial infarction in first degree relatives; odds ratios for myocardial infarction, given at least one reported relative or at least one verified relative being affected. RESULTS: 349 of the 400 probands provided detailed family histories, reporting on 2812 first degree relatives. The overall sensitivity, specificity, and positive predictive value of reported histories were 67.3%, 96.5%, and 70.5% for cases and 68.5%, 97.7%, and 73.8% for controls. The kappa coefficients were modest: 0.65 for cases and 0.68 for controls. The odds ratios for myocardial infarction, given at least one affected relative, were not substantially inflated by recall bias. Some recall bias was evident for the probands' reports of their siblings' histories of myocardial infarction, the odds ratio for a reported history being 1.67 (95% confidence interval 1.09 to 2.57) and for the validated history 1.54 (1.01 to 2.37). CONCLUSIONS: Although the relative risk of disease is correctly estimated, the predictive accuracy of a casual family history of myocardial infarction may limit the effectiveness of targeted screening programmes. They may, however, complement other strategies based on genetic testing.

Case-Control Studies↗
PubMed1993

Variant mapping of the Apo(B) AT rich minisatellite. Dependence on nucleotide sequence of the copy number variations. Instability of the non-canonical alleles.

Because of its variations in length, the AT rich Hyper-Variable Region (HVR) of the 3' end of the Apolipoprotein B gene is used as a polymorphic maker in genetic studies. It contains a SspI site in its repeated motif and we used this feature to precisely analyse the internal structure of the different alleles found at this locus in a Caucasian population. We performed total digestion on 194 alleles as well as Minisatellite Variant Repeat mapping (MVR mapping: partial digestion) on 54. The results show that the level of length variability (in copy number) of the 5' end of this locus is at least two times higher than that of the 3' end. This could be correlated with the difference in nucleotide sequence between the two parts of the HVR and suggests the dependence on the primary structure of the mechanism that produces length variability. A molecular model is proposed to explain this result. Moreover, the sharp analysis of the minisatellite structure by the distribution of SspI sites reveals differences between long and short alleles, indicating that in most cases, no recombination occurs between alleles of different sizes. Finally the rare alleles exhibit a non-canonical structure. These important points could explain the bimodal distribution of the frequencies of the alleles in the population.

Alleles↗
PubMed1993

Apolipoprotein B signal peptide polymorphism in patients with myocardial infarction and controls. "The ECTIM study".

We report the allele frequencies of the apolipoprotein B (Apo B) signal peptide polymorphism in patients with myocardial infarction and compare them with controls. The first sample consists of 197 myocardial infarction patients and 168 controls from Belfast (UK). The second sample consists of 167 myocardial infarction patients and 205 controls from Strasbourg (France), and the third consists of 71 patients and 146 controls from Haute-Garonne (Toulouse, France). No significant differences were observed in the frequency distribution of genotypes among cases and controls or between populations. However, there were more rare homozygotes in the Belfast cases. Significant associations were observed between the Apo B signal peptide polymorphism and mean levels of total cholesterol, low density lipoprotein cholesterol, Apo B and lipoprotein particles containing Apo (a) [Lp(a)] in the Strasbourg control population. Individuals homozygous for the rare allele had higher levels of these lipid parameters. In Belfast, although not statistically significant, the Apo B signal peptide polymorphism had a similar effect on Apo-B-related parameters as seen in Strasbourg. No significant associations were observed in the Haute-Garonne population where the risk of myocardial infarction is three times lower than in Belfast. In all three populations, the average Lp(a) levels were consistently different among Apo B signal peptide genotypes. These data implicate the Apo B signal peptide in determining some of the risks of myocardial infarction in these populations. Regardless of the exact mechanism, the Apo B signal peptide is an important candidate locus for the study of potentially atherogenic lipid variants.

Adult↗
PubMed1993

Polymorphisms of the apolipoprotein B and E genes and their relationship to plasma lipid variables in healthy Chinese men.

In this study we have analysed the apolipoprotein (Apo) E polymorphism and polymorphisms of the ApoB gene, including the ApoB/XbaI and ApoB/4311 diallelic polymorphisms and a hypervariable region (HVR) situated in the 3' region of the gene (ApoB/3'HVR), in a sample of healthy male subjects from Taiyuan (northern People's Republic of China). In comparison to Caucasian populations, in the Chinese sample, the XbaI2 allele (presence of cutting site; frequency 6.1%; and 95% confidence interval, 3.3-8.9) and the long HVR alleles (9.4%; 6.0-12.8) were rare, whereas the ApoB/4311 (Ser) allele (70.8%; 65.4-76.2) and the 34-repeat allele of the HVR (HVR34; 62.4%; 56.8-68.0) were frequent. In subjects having none, one, or two HVR34 alleles, the mean levels of plasma triglycerides were 2.32 +/- 1.44 (SD), 1.45 +/- 0.74, and 1.75 +/- 1.07 g/l, respectively (P < 0.007). Similar trends were observed for very low density lipoprotein (VLDL) cholesterol, LpE:B, and LpCIII:B. The frequencies of the ApoE alleles were similar to those reported in other populations of Asian origin; E2 (7.4%; 4.2-10.6), E3 (84.4%; 80.2-88.6), and E4 (8.2%; 5.0-11.4). Individuals carrying the E2 allele had a lower mean level of ApoB than E33 individuals: 0.87 +/- 0.16 and 1.00 +/- 0.22 g/l, respectively (P < 0.007). Individuals carrying the E4 allele had higher levels of ApoE than E33 individuals: 0.140 +/- 0.084 and 0.094 +/- 0.052 g/l, respectively (P < 0.004); similar trends were observed for VLDL cholesterol, triglycerides, LpE:B, and LpCIII:B. The ApoB/HVR34 and ApoE/E4 polymorphisms accounted for 10% to 15% of the variability of the plasma levels of VLDL cholesterol, ApoE, triglycerides, LpE:B, and LpCIII:B. Several lipid variables appeared to be favourably affected by specific forms of ApoB and ApoE that are particularly frequent in this Chinese population.

Adult↗
PubMed1993

Distribution of lipid variables in subjects in Belfast, Northern Ireland and Taiyuan, P R China.

To compare the plasma lipid, lipoprotein and apolipoprotein profiles of people of Chinese and European origin, a sample of 151 male Chinese subjects was selected from Taiyuan, Shanxi Province, P R China to 202 broadly age-matched subjects in Belfast who were selected as controls in a case-control study of myocardial infarction. Mean total cholesterol (TC) was 6.15 mmol/l in Belfast and 4.28 mmol/l in Taiyuan. Low density lipoprotein cholesterol (LDL) was much higher in Belfast. High density lipoprotein cholesterol (LDL) was also higher in Belfast than in Taiyuan but the ratio of HDL to TC was lower in Belfast than Taiyuan. Triglyceride (TG) levels were similar and this was reflected in the relatively high level of apolipoprotein E (apo E) in the Chinese sample.

Adult↗
PubMed1993

Inference of the strength of genotype-disease association from studies comparing offspring with and without parental history of disease.

The association between genetic polymorphisms and a multifactorial disease is generally investigated by case-control studies. However, inference about the genotype-disease association can also be drawn from studies comparing offspring having a parental history of disease with offspring having no parental history. In such studies, differences in genotype frequencies between the two groups of offspring will reflect a different transmission of alleles from affected and unaffected parents. We showed that in offspring studies, the odds ratios (ORs) associated with heterozygous and homozygous genotypes are related by the formula: OR(het) = (OR(hom) + 1)/2. These ORs depend only on the allele frequencies in affected and unaffected parents, and not on the pattern of genotype-disease association. Under simple patterns of association, it is possible to infer from the ORs observed among offspring, the expected ORs for the disease. The decrease of power of offspring studies by comparison with classical case-control studies is evaluated, and an application is given on the association between the apoE polymorphism and coronary heart disease.

Adult↗
PubMed1993

Genetic variation at the beta-fibrinogen locus in relation to plasma fibrinogen concentrations and risk of myocardial infarction. The ECTIM Study.

Increased plasma fibrinogen concentration is a major cardiovascular risk factor. Conflicting results on genetic variations in plasma fibrinogen levels have been reported. Furthermore, whether fibrinogen genotype is associated with the risk of ischemic heart disease has not been studied so far. An HaeIII restriction fragment length polymorphism of the beta-fibrinogen gene was used in a case-control study to investigate the genetic variation at this locus in relation to plasma fibrinogen concentrations and the risk of myocardial infarction (MI). Five hundred thirty-three male patients aged 27-66 years and 648 control subjects were recruited from four World Health Organization MONICA centers in Northern Ireland and in France. The absence of the HaeIII cutting site (H2 allele) was associated with a significant rise in fibrinogen concentrations in both patients and control subjects. The effect of the HaeIII polymorphism on plasma fibrinogen levels did not significantly differ between centers. Fibrinogen levels were higher in smokers than in nonsmokers. The difference between the two groups was larger in subjects with the genotype H2H2 than in those with either genotype H1H1 or H1H2, regardless of the case-control status. However, there was no significant interaction between smoking status and genotype in their effects on variance in fibrinogen levels, whereas fibrinogen levels. HaeIII genotype accounted for approximately 1% of the total variance in fibrinogen levels, whereas smoking and age together explained 7% and 5% in control subjects and patients, respectively. The frequency of the H2 allele was 0.21 in control subjects and 0.19 in patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Hypocaloric diet and antihypertensive drug treatment. A randomized controlled clinical trial.

OBJECTIVE: To compare the amount of drug quantified by a score needed to control blood pressure in two groups of overweight hypertensive patients, receiving or not receiving a hypocaloric diet. DESIGN: Randomized controlled clinical trial. SETTING: Two hospital outpatient hypertension clinics. PATIENTS: Fifty-four subjects with a DBP between 95 and 110 mmHg and a weight > or = 110% of the ideal weight. INTERVENTION: Allocation to either drug treatment (DT) or hypocaloric diet (HD). In the HD group, after 2 months, an antihypertensive drug was administered to the subjects with a DBP > or = 90 mmHg, following the same scheme protocol as in the DT group. Subjects were followed during 10 months by a clinician only in the DT group and by a clinician and a dietician in the HD group. MAIN OUTCOME MEASURES: Score of treatment: hydrochlorothiazide 25 mg [score = 1] with, as needed to obtain a DBP < 90 mmHg, the addiction of enalapril 10 mg [score = 2], 20 mg [score = 3], and nifedipine 40 mg [score = 4]. RESULTS: At the end of the trial, 5 subjects were lost to follow-up in the HD group and 1 in the DT group (p > 0.05). Mean weight loss was 5.9 kg (sd = 1.2) in the HD and 2.3 kg (sd = 0.7) in the DT group (p = 0.02). Mean decrease in DBP was 18 mmHg (sd = 7) and 15 mmHg (sd = 8) in HD and DT groups respectively (p = 0.36). Mean DBP was 84 mmHg (sd = 7.8) in the HD group and 85 mmHg (sd = 7.2) in the DT group. In the HD group, 8 (38.1%) subjects had a DBP < 90 mmHg without any drug treatment. The mean drug treatment score was 0.86 (sd = 0.91) in the HD and 1.52 (0.70) in the DT group (p = 0.01). CONCLUSION: This study shows that in overweight hypertensives, the quantity of drug needed to achieve an acceptable level of BP is nearly reduced by 50% when an efficient hypocaloric diet is prescribed simultaneously.

Adult↗
PubMed1992

Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction.

Factors involved in the pathogenesis of atherosclerosis, thrombosis and vasoconstriction contribute to the development of coronary heart disease. In a study comparing patients after myocardial infarction with controls, we have explored a possible association between coronary heart disease and a variation found in the gene encoding angiotensin-converting enzyme (ACE). The polymorphism ACE/ID is strongly associated with the level of circulating enzyme. This enzyme plays a key role in the production of angiotensin II and in the catabolism of bradykinin, two peptides involved in the modulation of vascular tone and in the proliferation of smooth muscle cells. Here we report that the DD genotype, which is associated with higher levels of circulating ACE than the ID and II genotypes, is significantly more frequent in patients with myocardial infarction (n = 610) than in controls (n = 733) (P = 0.007), especially among subjects with low body-mass index and low plasma levels of ApoB (P < 0.0001). The ACE/ID polymorphism seems to be a potent risk factor of coronary heart disease in subjects formerly considered to be at low risk according to common criteria.

Adult↗
PubMed1992

Segregation analysis of height-adjusted weight with generation- and age-dependent effects: the Nancy Family Study.

A segregation analysis using a regressive model with generation- and age-dependent effects was applied to familial data of height-adjusted weight to investigate the major gene hypothesis. The sample included 629 nuclear families with 2,534 members volunteering for a free health check-up in the Preventive Medicine Center of Vandoeuvre-lès-Nancy, France. The familial correlations were 0.094 +/- 0.040 between spouses, 0.198 +/- 0.023 between parent and offspring, and 0.327 +/- 0.034 between siblings. The variability of the trait was higher in parents than in offspring. The most parsimonious genetic model indicated a codominant major effect increasing with age in childhood, then stabilizing in adulthood. The same data were analyzed using the classical mixed model, assuming equality of variances between parents and offspring, no resemblance between spouses, similar parent-offspring and sib-sib correlations, and identical effects in parents and offspring. This analysis indicated a recessive solution. In both analyses, mendelian transmission was rejected. However, the mixture of two distributions in the recessive model, instead of three in the codominant one, was less constraining with respect to the test of transmission probabilities, and the rejection of mendelian transmission was due to a single family in the recessive case, instead of several families in the codominant one. This could possibly explain why previous studies, all using the mixed model, found evidence for a recessive major gene. Although the major gene hypothesis cannot be definitely ruled out from our results, the mechanism appears more complex than the effect of one single gene.

Adolescent↗
PubMed1992

A very conservative region of ApoB-100 in the putative binding region to the LDL receptor in the Toulouse population.

The nucleotide sequence of the putative binding site of ApoB-100 was studied in Hypercholesterolemic IIa patients and controls from the Toulouse area. Only one patient possesses the 3,500 mutation, which is responsible for defective familial hypercholesterolemia. The other individuals (including 39 patients and 14 controls) display the same nucleotide sequence although four nucleotide substitutions have been described in this region. This homogeneity of the Toulouse population in the putative binding site of ApoB-100 is discussed.

Adult↗
PubMed1992

Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels.

The hypothesis of a genetic control of plasma angiotensin I-converting enzyme (ACE) level has been suggested both by segregation analysis and by the identification of an insertion/deletion (I/D) polymorphism of the ACE gene, a polymorphism contributing much to the variability of ACE level. To elucidate whether the I/D polymorphism was directly involved in the genetic regulation, plasma ACE activity and genotype for the I/D polymorphism were both measured in a sample of 98 healthy nuclear families. The pattern of familial correlations of ACE level was compatible with a zero correlation between spouses and equal parent-offspring and sib-sib correlations (.24 +/- .04). A segregation analysis indicated that this familial resemblance could be entirely explained by the transmission of a codominant major gene. The I/D polymorphism was associated with marked differences of ACE levels, although these differences were less pronounced than those observed in the segregation analysis. After adjustment for the polymorphism effects, the residual heritability (.280 +/- .096) was significant. Finally, a combined segregation and linkage analysis provided evidence that the major-gene effect was due to a variant of the ACE gene, in strong linkage disequilibrium with the I/D polymorphism. The marker allele I appeared always associated with the major-gene allele s characterized by lower ACE levels. The frequency of allele I was .431 +/- .025, and that of major allele s was .557 +/- .041. The major gene had codominant effects equal to 1.3 residual SDs and accounted for 44% of the total variability of ACE level, as compared with 28% for the I/D polymorphism.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗