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Biomedical subjects

T Brousseau

Publications and source records attributed to T Brousseau.

16 recordsLinked to original sources
PubMed2003

Allelic variation in the promoter region of the LDL receptor gene: analysis of an African-specific variant in the FP2 cis-acting regulatory element.

DNA samples of 2303 individuals from nine different population groups were screened for variant -175g-->t in the promoter region of the low-density lipoprotein receptor (LDLR) gene. The -175g-->t variant detected at carrier frequencies of 3-10% in different African population groups was absent in the Caucasian and Asian (Chinese) individuals studied. In contrast to previous findings in Black South Africans where this polymorphism predominated in patients with familial hypercholesterolaemia (FH), it occurred at a significantly lower frequency in hypercholesterolaemics from the recently admixed Coloured population of South Africa compared with population-matched controls (P<0.0001). Haplotype and mutation analysis excluded the likelihood that this finding is due to association with a specific disease-related mutation in FH patients, although reversal of the positive association with FH observed in the Black population may, at least in part, be due to admixture linkage disequilibrium. Transient transfection studies in HepG2 cells demonstrated that the -175t allele is associated with a non-significant decrease ( approximately 7%) of LDLR transcription in the absence of sterols. The data presented in this study raise the possibility that the -175g-->t polymorphism may have subtle effects that become clinically important within certain genetic and/or environmental contexts.

Alleles↗
PubMed2001

Blood lipid concentrations and risk of myocardial infarction.

In western countries, individuals with plasma lipid concentrations above a set threshold value are judged to be at risk of coronary heart disease. However, in Algeria, people tend to have lower lipid concentrations than those in the developed world, and might, therefore, be excluded from preventive strategies and denied treatment. We did a study in Algeria in which we investigated the plasma lipid profiles of 67 individuals who had had a myocardial infarction, and 70 controls. We compared our results with those of two other similar studies done in France and Ireland. An increase in concentration of total cholesterol and LDL cholesterol, and a decrease in HDL cholesterol, was associated with raised risk of myocardial infarction in our study, but lipid concentrations rarely reached the recommended threshold values. However, cholesterol ratios (total/HDL, LDL/HDL) provided consistent and comparable estimates of cardiovascular risk across the three populations. Our results raise the question of whether threshold recommendations for cardiovascular risk prevention, in populations with low concentration of plasma lipids, should be made.

Adult↗
PubMed2000

Independent association of an APOE gene promoter polymorphism with increased risk of myocardial infarction and decreased APOE plasma concentrations-the ECTIM study.

Apolipoprotein E (APOE) is a major protein in lipid metabolism existing in three common isoforms: APOE2, -3 and -4. The varepsilon4 allele of the APOE gene ( APOE ) coding for the APOE4 isoform is associated with an increased risk of myocardial infarction (MI) and of Alzheimer's disease (AD). Recently, several polymorphisms in the APOE regulatory region have been reported. Some of these have been associated with AD and modified APOE allelic mRNA expression in AD brains. Here, we have investigated whether three of these promoter polymorphisms (-491AT, -427CT and -219GT) can also modify cardiovascular risk. The hypothesis was tested in a large multicentre case-control study of MI, the ECTIM Study, on 567 cases and 678 controls. Among the three APOE promoter polymorphisms tested, only the-219T allele was associated with a significantly increased risk of MI (OR = 1.29, 95% CI: 1.09-1.52, P < 0.003) and the effect was shown to be independent of the presence of the other mutations, including the APOE epsilon2/epsilon3/epsilon4 polymorphism. Moreover, the-219T allele greatly decreased the APOE plasma concentrations in a dose-dependent manner ( P < 0.008). These data indicate that the-219GT polymorphism of the APOE regulatory region emerges as a new genetic susceptibility risk factor for MI and constitutes another common risk factor for both neurodegenerative and cardiovascular diseases.

Adult↗
PubMed1999

Risk of dementia in parents of probands with and without the apolipoprotein E4 allele. The EVA study.

STUDY OBJECTIVE: Age, family history of dementia and the epsilon 4 allele of the apolipoprotein E gene have been associated with Alzheimer's disease (AD). Considering the strength of APOE-epsilon 4 as a genetic risk factor for AD, this factor might explain a large part of the association between AD and a family history of dementia. Therefore, in the general population, a higher frequency of dementia should be observed among parents of probands with at least one epsilon 4 allele than in parents of probands without this allele. DESIGN, SETTING, AND PARTICIPANTS: The study investigated a sample of 1153 volunteers between 59 and 71 years old, genotyped for the APOE gene, all participating in the EVA study. Dementia in their parents was determined using a self reported questionnaire. MAIN RESULTS: The frequency of dementia in 2164 parents was examined and it was found that 245 were demented. The percentage of demented parents was 13.0% in the subgroup of parents of subjects having one or two epsilon 4 alleles and 10.8% in the other subgroup. The relative risk of dementia among parents according to the APOE-epsilon 4 status of probands, was calculated using a Cox model adjusted for the educational level of parents and their history of stroke: RR = 1.21 (95% CI 0.90, 1.63). CONCLUSION: This lack of association supports the observation that in the general population, APOE-epsilon 4 cannot explain a large part of family history of dementia.

Aged↗
PubMed1999

[Genetics and therapeutic intervention].

Elucidating the molecular mechanisms involved in metabolic diseases can, in many cases, characterize individual susceptibility resulting from mutations altering genetic inheritance. Better knowledge of this genetic component emphasizes the importance of revising disease classifications and diagnostic procedures which are currently based on phenotypic examination and may result in heterogeneous groupings of patients with different etiologies. By taking into account interindividual variability of therapeutic response, a new field of pharmacology, called Pharmacogenetics, may help evaluate and optimize therapeutic procedures in more homogeneous groups of patients.

Genetic Diseases, Inborn↗
PubMed1996

Early effect of ApoE-epsilon 4 allele on cognitive results in a group of highly performing subjects: the EVA study. Etude sur le Vieillissement Artériel.

We examined the association between apolipoprotein E (ApoE) epsilon 4 allele and cognitive performances in a population sample of 1174 high functioning volunteers aged 59-71 years. The neuropsychological battery included the Mini Mental State Examination (MMSE) and nine tests assessing visual attention, verbal memory, visual processing, logical reasoning, psychomotor rapidity, visual memory, auditory attention and verbal fluency. The ratio of genotypes with zero, one or two epsilon 4 alleles was 70.6%, 21.4% and 1.9%, respectively. The epsilon 4 allele was significantly associated with lower scores for visual attention, psychomotor rapidity and MMSE. In the best performer subgroup (MMSE score above 25, n = 1028), all relationships persisted. Our findings demonstrate that the ApoE-epsilon 4 allele is early associated with low normal cognitive performances in areas which are not specifically affected at the subclinical onset of dementia.

Aged↗
PubMed1995

[Detection of the Arg 3500-->Gln mutation of B apolipoprotein. Value in clinical practice].

OBJECTIVE: Familial defective apolipoprotein B-100, caused by a mutation in position 3500 of apolipoprotein B, induces hypercholesterolaemia, a major risk factor of coronary artery disease. The objective is to evaluate the interest of the detecting subjects bearing the Arg3500-->Gln mutation and to observe the response of these subjects to different physiological and therapeutic situations, in clinical practice. METHODS: We performed a systematic screening among hypercholesterolaemic outpatients attending a lipid clinic. The heterozygote subjects were followed up during more than one year and, in some of them, we compared the efficiency of cholesterol-lowering drugs belonging to the different classes: fibrate and statine. RESULTS: Two probands and 3 related subjects were detected. Three patients were treated. For two patients, reduction of LDL-cholesterol plasma levels was observed with both drugs but was significantly higher with statine than with fibrate. For the third one, carrying the E2E4 phenotype, the statine did not seemed to have a major effect. CONCLUSION: The number of probands is in agreement with the frequency reported in literature. A possible interaction of the effect of statine with the apo E2 isoform is discussed.

Adult↗
PubMed1994

Evidence of non-deficient low-density lipoprotein receptor patients in a pool of subjects with clinical familial hypercholesterolemia profile.

For this study, we selected 41 adult patients with the classic clinical diagnosis of heterozygous familial hypercholesterolemia (FH), which is characterized by a low-density lipoprotein (LDL) cholesterol level above the 95th percentile, xanthomas, and/or personal or familial cardiovascular history. We used an indirect immunocytofluorimetric assay to classify these 41 subjects according to LDL receptor function on lymphocytes. We found that LDL receptor activity was normal in nine patients. A large study of plasma lipid, lipoprotein, and apolipoprotein levels found no significant difference between patients with and without LDL receptor defect. Familial defective apolipoprotein (apo) B-100 (FDB) and LDL-binding defects were not found in the nine patients without LDL receptor defect. These results suggest that other defects in the regulation of lipoprotein metabolism are capable of giving rise to a clinical and biochemical disorder indistinguishable from classic FH.

Adult↗
PubMed1994

Apolipoprotein E, epsilon 4 allele as a major risk factor for sporadic early and late-onset forms of Alzheimer's disease: analysis of the 19q13.2 chromosomal region.

An association between the 19q13.2 chromosomal region and Alzheimer's disease (AD) has been reported in AD families and for sporadic AD. Recent observations provide evidence that the epsilon 4 allele of the apolipoprotein E gene (APOE), located in this region, is a risk factor for late-onset AD. Within this region, other genes possibly involved in the pathophysiology of AD and in strong linkage disequilibrium with the APOE locus may be responsible for this association. To test this hypothesis, we analysed the allelic distribution of four polymorphic genetic markers flanking the APOE gene (D19S178 (CA)n repeat, D19S47 (CA)n repeat, APOCI HpaI restriction fragment length polymorphism, APOCII (CA)n repeat). We performed these analyses in a sample of late-onset sporadic cases (n = 36) versus controls (n = 38), and in a sample of early-onset sporadic cases (n = 34) versus controls (n = 36). Early-onset cases were analysed for two cut-offs with late-onset: less than 60 and less than 65. We observed a significant increased frequency of the APOE epsilon 4 allele in late-onset and early-onset AD with ages at onset less than 60 and less than 65. The adjusted odds ratio (OR) of the bearers of at least one APOE epsilon 4 allele was 4.10 ([1.84;9.16]) when estimated in both populations with a logistic regression model. Surprisingly, the odds ratio of the bearers of at least one APOE epsilon 2 allele was also significant and equal to 0.11 ([0.02;0.50]) suggesting a possible protective effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Age of Onset↗
PubMed1994

Confirmation of the epsilon 4 allele of the apolipoprotein E gene as a risk factor for late-onset Alzheimer's disease.

Family studies indicate a possible linkage between the q13.2 region of chromosome 19 and Alzheimer's disease (AD). An isoform of apolipoprotein E, whose gene maps in this region, is more frequent in AD. In this study, we investigated the possible association of a genetic polymorphism of the apolipoprotein E gene with late-onset AD. We compared apolipoprotein E polymorphism distribution between patients with sporadic late-onset AD (n = 36) and controls of the same age (n = 38). Individuals carrying at least one epsilon 4 allele were present in 41.7% of the patients, compared with only 10.5% of the controls (p < 0.001). This result indicates an association between late-onset AD and the 19q13.2 region containing the apolipoprotein E gene locus.

Age Factors↗
PubMed1993

Sequential ultracentrifugation micromethod for separation of serum lipoproteins and assays of lipids, apolipoproteins, and lipoprotein particles.

We describe a fast sequential separation of very-low-density, low-density, and high-density lipoproteins from 400 microL of serum, using the Beckman TL100 ultracentrifuge. The cumulative centrifugation time is 9.5 h. The purity of lipoprotein fractions was verified by a gel-filtration procedure. The major contaminant is the serum albumin, which can be eliminated by a second centrifugation at the same density. Enzymatic measurement of lipids shows good recovery (> 91%) and weak within-sample variation (< 7%). In comparison with a density-gradient procedure, the deleterious effects on the lipoprotein structure appear to be limited, as shown by the low concentrations of apolipoprotein (apo) E and apo A-I in the fraction > 1.21 kg/L. Furthermore, the micro-ultracentrifugation also gives a better recovery rate. Finally, we have studied the distribution of lipids, apolipoproteins, and lipoprotein particles (LpA-I:A-II, LpB:C-III, LpB:E) in each fraction separated from 10 serum samples from healthy subjects.

Adult↗