[Declared knowledge, beliefs and practices for cardiovascular disease prevention in the French population].
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Adult↗
Biomedical subjects
D Arveiler
Publications and source records attributed to D Arveiler.
Prevalence of type 2 diabetes and impaired fasting glucose in the middle-aged population of three French regions - The MONICA study 1995-97.
OBJECTIVES: The aim of this study was to determine the prevalence of type 2 diabetes and impaired fasting glucose (IFG) in a population-based sample of 3 508 subjects, aged 35-64 years, participating in the French MONICA population survey from 1995 to 1997 in three French regions: the Urban Community of Lille, the Bas-Rhin and the Haute-Garonne. MATERIAL AND METHODS: Previously diagnosed type 2 diabetes is defined by the current use of oral hypoglycaemic treatment and newly diagnosed subjects by fasting plasma glucose (FPG) > or =7.0 mmol/L according to the ADA 1997 recommendations. IFG was determined by 6.1< or =FPG< or =6.9 mmol/L. Adjusted prevalences are calculated according to the French 1990 census data. RESULTS: Type 2 diabetes adjusted prevalence is 5.1% [4.1-6.1] in women and 7.3% [6.1-8.4] in men while IFG adjusted prevalence is 5.2% [4.2-6.2] and 11.8% [10.3-13.4] respectively. Prevalences of type 2 diabetes and IFG are both significantly higher in men than in women. This trend appears in any age group for IFG, but is only observed in 55-64 year-old subjects for type 2 diabetes. The reduction of the FPG threshold to screen diabetes mellitus from 7.8 to 7.0 mmol/L according to the ADA recommendations results in a 2.2-fold increase in the number of newly diagnosed diabetic subjects, screened by one FPG measurement, in our population-based sample. CONCLUSIONS: The MONICA population survey confirms that type 2 diabetes represents a major health care problem in France and underlines the influence of gender on the prevalence of both type 2 diabetes and IFG in the French middle-aged population.
Adult↗
Influence of parental histories of cardiovascular risk factors on risk factor clusters in the offspring.
OBJECTIVES: To assess the effect of parental histories of cardiovascular risk factors on risk factor clusters (RFC) in representative samples from three French populations (MONICA centers of Lille, Strasbourg, Toulouse). MATERIAL AND METHODS: In a representative cross-sectional study, we screened 1,291 males and 1,264 females, aged 35-64 years. Subjects were defined as RFC cases when they were affected by at least 2 disorders among, hypertension (systolic or diastolic blood pressure >=140/90 mmHg and/or antihypertensive drug), diabetes (physician-diagnosed diabetes and/or glycemia >=7.0 mmol/l and/or hypoglycemic drug), and dyslipidemia (triglycerides > 2.26 mmol/l and/or HDL-cholesterol<0.9 mmol/l in men and<1.2 mmol/l in women). Nineteen percent of the subjects were RFC cases. Parental histories of cardiovascular risk factors (hypertension, diabetes, hyperlipidemia) were positive if they were under 65. About 29% of the subjects had at least one parental history of risk factor. RESULTS: After adjustment for sex, age, educational level, sedentary lifestyle, alcohol consumption, body mass index, LDL cholesterol and center, parental histories of cardiovascular risk factors were significantly associated with the RFC. One, two, or at least three parental histories were significantly associated with increased odds of being RFC cases (adjusted OR 1.39 95% CI [1.05-1.82], 2.90 95% CI [1.91-4.40], 2.93 95% CI [1.41-6.08]). Furthermore, a maternal-only history vs a paternal-only history of hypertension or diabetes was associated with strong odds of being an RFC case. CONCLUSION: At least a single cardiovascular risk factor in parents was significantly associated with RFC in offspring, independently of environmental parameters.
Adult↗
[Cost of cardiovascular risk factor prevention in middle-aged French men. The PRIME study].
BACKGROUND: Little is known regarding the cost of cardiovascular risk factor prevention in France. In this study, we assessed the cost of antihypertensive and hypolipidaemic drug treatment in middle-aged French men without history of coronary heart disease. METHODS: A cross-sectional study was conducted between 1991 and 1993 in 1606 subjects treated for hypertension or dyslipidaemia from the three French centres participating in the PRIME study. The daily cost of treatment (in Euros) was assessed using data from the Agence Nationale du Médicament. RESULTS: Mean daily cost of hypertension was 0.65 euro per patient; after multivariate adjustment, obese subjects had a mean daily cost of 0.74+/-0.03 euro (adjusted mean +/- standard error) versus 0.66+/-0.03 euro for non-obese (p<0.001). Only 58% of hypertensive subjects were adequately controlled, and this percentage was higher in the Toulouse centre (80.1%) than in Lille (44.4%) or Strasbourg (50.2%), p<0.001. Fibrates were the most frequently prescribed hypolipidemic drug; nevertheless, prescription of statins was higher than fibrates in the Toulouse centre, which led to a higher mean daily cost for dyslipidaemia, which was further confirmed by multivariate adjustment: 0.59+/-0.05 euro (adjusted mean +/- standard error) in Toulouse versus 0.44+/-0.04 euro in Lille and 0.44+/-0.04 euro in Strasbourg. Only 54% of treated dyslipidemic subjects had their lipid levels within normal values, and this percentage was significantly lower (44%) in Strasbourg than in Lille (58%) or Toulouse (59%) (p<0.001). CONCLUSION: The prescription of anti-hypertensive or hypolipidemic drugs differs according to centre, leading to significant differences in mean daily cost of treatment. A considerable percentage of treated subjects is not adequately controlled, with possible consequences at the economical level.
Alcohol Drinking↗
Associations between classical cardiovascular risk factors and coronary artery disease in two countries at contrasting risk for myocardial infarction: the PRIME study.
PURPOSE: In two countries with contrasting risk for coronary artery disease (CAD)-Northern Ireland and France-a case-control study was performed on baseline data within a cohort study to compare the strength of the associations between CAD prevalence and classical risk factors. METHOD AND RESULTS: A sample of 9561 men, aged 50-60 years, was studied: 382 had had myocardial infarction or angina, and 9179 were controls. In both countries, variables associated with CAD were age, body mass index, hypertension, diabetes, family history of myocardial infarction (MI), tobacco consumption, triglycerides, HDL-cholesterol, apolipoprotein A-I and B levels. Logistic regression analyses were conducted using standardized odds ratios. The strength of the associations with CAD was rather similar in the two countries (Northern Ireland versus France) for age [1.26 (1.10-1. 45) vs. 1.41 (1.17-1.69)], family history of MI [1.50 (1.04-2.15) vs. 1.83 (0.99-3.37)], hypertension [1.49 (1.13-1.97) vs. 1.67 (1.14-2. 44)], diabetes [5.42 (2.53-11.60) vs. 2.24 (1.06-4.73)], tobacco consumption [1.43 (1.27-1.60) vs. 1.39 (1.22-1.58)], HDL-cholesterol [0.80 (0.68-0.94) vs. 0.86 (0.70-1.06)] and triglyceride levels [1. 17 (1.01-1.36) vs. 1.10 (0.91-1.32)]. Discrepancies concerned lipoprotein(a) [1.22 (1.06-1.40) vs. 0.96 (0.81-1.15), P<0.01], with stronger associations in Northern Ireland than in France. CONCLUSION: It is concluded that the higher prevalence of CAD in Northern Ireland cannot be explained by major differences in the susceptibility to classical risk factors; the difference in risk of CAD appears mainly related in Northern Ireland to other risk factors including a worse lipid profile and genetic/environmental interactions.
Apolipoproteins↗
Why mortality from heart disease is low in France. Rates of coronary events are similar in France and Southern Europe.
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Adult↗
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↗
Extensive association analysis between the CETP gene and coronary heart disease phenotypes reveals several putative functional polymorphisms and gene-environment interaction.
An extensive association analysis of a candidate gene for coronary heart disease, Cholesteryl Ester Transfer Protein (CETP) gene, was performed. Ten polymorphisms, out of which three were newly identified in regulatory regions, were investigated for association with myocardial infarction (MI) and 2 MI endophenotypes (CETP mass and HDL-cholesterol level) in 568 MI patients and 668 controls. The polymorphisms affecting codon 405 (Ile(405)Val) and the nucleotide 524 downstream from the stop codon (G(+524)T) were almost completely concordant and associated with plasma CETP mass (P < 0.001). The polymorphisms -629 (located in promoter), intron1 (Taq1B) and intron7 were almost completely concordant and associated with plasma CETP mass (P < 0.0001) and HDL-cholesterol levels (P < 0.0001). This latter association was not found in teetotalers and increased with the quantity of alcohol consumed. Heavy drinkers (>75g/day) homozygous for the (-628)A allele had a reduced risk of MI (OR = 0. 33, P < 0.02). Subjects both homozygous for (451)Arg and heterozygous for (373)Pro had decreased plasma HDL-cholesterol levels and this effect increased with alcohol consumption. The results illustrate the complexity of polymorphism-phenotype associations. They suggest that the CETP gene may carry several functional polymorphisms. Observed interactions between alcohol consumption and polymorphisms associated with HDL-cholesterol level constitute concrete examples of gene-environment interactions. Furthermore, the pattern of association between HDL-cholesterol levels and the polymorphisms at codons 373 and 451 illustrated how two polymorphisms may be confounders (in the usual epidemiological sense) one for the other: their marginal effects are neutralized because of linkage disequilibrium and thus are not detectable by standard univariate association analysis.
Adult↗
Identification of two polymorphisms in the early growth response protein-1 gene: possible association with lipid variables.
Early growth response factor (EGR)-1 may play an important role in the development of atherosclerosis by inducing the expression of several relevant genes which contribute to the complex modulation of vascular structure and function, leading to vascular occlusive lesions. To investigate the possible role of molecular variants in the human EGR-1 gene for the predisposition to atherosclerosis or coronary heart disease we screened the 5'- and 3'- flanking regions and the entire coding sequence for polymorphisms by polymerase chain reaction/single-strand conformation polymorphism analysis and sequencing. Male patients (n=615) with myocardial infarction and 720 age-matched, male control subjects of the Etude Cas-Témoin de l'Infarctus du Myocarde were genotyped for two newly identified polymorphisms in the 5'- (C-151T) and 3'- (T+861C) flanking region of the EGR-1 gene using hybridization with allele-specific oligonucleotides. Allele and genotype frequencies did not significantly differ between patients with myocardial infarction and control subjects without coronary heart disease. In controls not taking hypolipidemic drugs there was a significant association of the -151T allele with lower plasma levels of total cholesterol (P=0.029), low-density lipoprotein cholesterol (P=0.025) and apolipoprotein B (P=0.038) and a higher ratio of high-density to low-density lipoprotein (P=0.049) than with the C-151 allele. We conclude that the C-151T polymorphism of the EGR-1 gene may contribute to modifications of the lipid metabolism. Our findings need to be replicated in independent studies, and in vitro promoter studies should evaluate the functional consequence of the -151T allele, which disrupts a consensus core sequence for the ubiquitous transcription factor activator protein 4.
Adult↗
Polymorphisms in the genes encoding platelet-derived growth factor A and alpha receptor.
Platelet-derived growth factors (PDGFs) may play an important role in the development of atherosclerosis acting as chemoattractants and mitogens for vascular smooth muscle cells and macrophages. Three dimeric forms of PDGF (AA, AB, BB) have different activities due to distinct binding properties mediated by two types of PDGF receptors (Ralpha, Rbeta). To investigate the possible contribution of molecular variants in the human PDGF-A and PDGF-Ralpha genes to coronary heart disease we screened these genes for polymorphisms by polymerase chain reaction/single-strand conformation polymorphism analysis. A total of 600 men with myocardial infarction and 717 age-matched male controls from four populations in Northern Ireland and France (the ECTIM Study) were gneotyped for newly identified polymorphisms in the genes encoding PDGF-A (C-26IN3T, H69H, C+12IN5T) and PDGF-Ralpha [-1630 I/D (+/-AACTT), A-1506G, C-1390G, G-956A, C-908A, G-793T, +69 I/D (+/-GA)] using allele-specific oligonucleotides. All PDGF-Ralpha polymorphisms, except C-908A, involving a nucleotide change in a common consensus site for GCF and SP-1 transcription factors, were in nearly complete association, generating two major haplotypes. The PDGF-A and PDGF-Ralpha polymorphisms provided a heterozygosity of 0.69 and 0.40, respectively. Genotype and allele frequencies of the PDGF-A and PDGF-Ralpha polymorphisms did not differ between patients with myocardial infarction and controls in either country. None of the polymorphisms investigated was associated with blood pressure, coronary artery stenosis, or any biochemical parameter available in the ECTIM Study.
Adult↗
The relationship between apolipoprotein AI-containing lipoprotein fractions and environmental factors: the prospective epidemiological study of myocardial infarction (PRIME study).
Apolipoprotein (apo) AI is distributed within high-density lipoproteins (HDL) between different types of particles, one containing both apoAI and apoAII (LpAI:AII), the other containing no apoAII (LpAI). We investigated the associations between LpAI and LpAI:AII with several factors such as body mass index (BMI), waist to hip ratio (WHR), alcohol intake, cigarette consumption and physical activity, in three French and one Northern Irish male populations included in a prospective study (PRIME study). LpAI and LpAI:AII were associated with variations in all environmental factors, except LpAI:AII, which was not associated with WHR. These relationships were unchanged after adjustment for other environmental factors, but slightly modified after adjustment for triglyceride levels. LpAI decreased when BMI, WHR and cigarette smoking increased, and increased with alcohol consumption and physical activity. LpAI:AII had a similar variation except for the absence of LpAI:AII modification associated with WHR variation. The associations between LpAI and BMI, alcohol consumption and cigarette smoking were largely dependent on HDL-cholesterol as indicated by the lack of any significance when the adjustment for HDL-cholesterol was made. Conversely, after adjustment for HDL-cholesterol, the significant association between LpAI:AII and BMI disappeared, while the associations between LpAI:AII and alcohol consumption, cigarette smoking and physical activity remained significant. These results suggest that the mechanisms of LpAI and LpAI:AII modulations differ according to each environmental factor, some dependent on the lipid content of lipoproteins and others not, but LpAI and LpAI:AII levels seem independent of triglyceride concentration.
Alcohol Drinking↗
The North-East-South gradient of coronary heart disease mortality and case fatality rates in France is consistent with a similar gradient in risk factor clusters.
In France, the mortality and case fatality rates of coronary heart disease follow a decreasing North-East-South gradient. The aim of the study was to evaluate the contribution of major cardiovascular risk factors to this gradient. To this end, the results of the third population survey of the WHO-MONICA Project conducted in three French geographically contrasted regions (the Urban Community of Lille in the North, the district of Bas-Rhin in the East and the district of Haute-Garonne in the South) are presented. One thousand seven hundred seventy-eight men and 1730 women aged 35-64 years were randomly selected from the electoral rolls. Major coronary heart disease risk factors (hypertension, hypercholesterolemia, low high-density lipoprotein (HDL)-cholesterol, obesity, smoking, physical inactivity, diabetes) were studied. The results show that the distribution of major coronary heart disease risk factors is heterogeneous among geographical areas in France. However, the proportion of subjects with more than three risk factors is higher in the North than in the other regions and the number of subjects with no risk factor is higher in the South than in the other areas. This distribution of risk factors among regions supports the hypothesis that accumulation of coronary heart disease risk factors contributes to the decreasing North-East-South gradient of cardiovascular mortality rates in France.
Adult↗
Characteristics of male vitamin supplement users aged 50-59 years in France and Northern Ireland: the PRIME Study. Prospective Epidemiological Study of Myocardial Infarction.
The prevalence and characteristics of vitamin supplement users were assessed in 7538 male subjects aged 50-59 from France and 2468 from Northern Ireland. In France, 15% of subjects used vitamin supplements; users were significantly younger, had a lower body mass index, a higher educational level, had more frequently a hard physical job, reported more frequently a personal history of disease and were less frequently retired or inactive than non-users. In Northern Ireland, 21% of subjects were vitamin supplement users; users had a lower body mass index, drank less alcohol, had a higher educational level, were more frequently non-smokers and professionally active, and reported a hard physical job and the practice of leisure sports more frequently than non-users. Finally, vitamin supplement users in Northern Ireland had a lower consumption of alcohol, smoked less, had a lower frequency of personal history of disease and were more frequently on dietary therapy for hypertension or dyslipidaemia than their French counterparts. We conclude that vitamin supplement use is associated with a healthier lifestyle and with dietary measures against hypertension and dyslipidaemia in Northern Ireland. The less favorable lifestyle observed for vitamin supplement users in France awaits further investigation.
Cross-Cultural Comparison↗
Patterns of alcohol consumption in middle-aged men from France and Northern Ireland. The PRIME study.
OBJECTIVE: To assess the patterns of alcohol consumption in France and Northern Ireland. DESIGN: Four cross-sectional studies. SETTING: Sample of 50-59 y old men living in France and Northern Ireland, consuming at least one unit of alcoholic beverage per week. SUBJECTS: 5363 subjects from France and 1367 from Northern Ireland. INTERVENTIONS: None. RESULTS: Consumption of wine was higher in France whereas consumption of beer and spirits was higher in Northern Ireland. Alcohol drinking was rather homogeneous throughout the week in France, whereas Fridays and Saturdays accounted for 60% of total alcohol consumption in Northern Ireland. In both countries, current smokers had a higher consumption of all types of alcoholic beverages than non-smokers. Similarly, obese and hypertensive subjects had a higher total alcohol consumption than non-obese or normotensive subjects, but the type of alcoholic beverages differed between countries. In Northern Ireland, subjects which reported some physical activity consumed significantly less alcoholic beverages than sedentary subjects, whereas no differences were found in France. Conversely, subjects with dyslipidemia consumed more alcoholic beverages than normolipidemic subjects in France, whereas no differences were found in Northern Ireland. In France, total alcohol, wine and beer consumption was negatively related to socioeconomic status and educational level. In Northern Ireland, total alcohol, beer and spirits consumption was negatively related whereas wine consumption was positively related to socioeconomic status and educational level. CONCLUSIONS: Alcohol drinking patterns differ between France and Northern Ireland, and also according to cardiovascular risk factors, socioeconomic and educational levels. SPONSORSHIP: Merck, Sharp & Dohme-Chibret (France), the NICHSA and the Department of Health and Social Service (Northern Ireland).
Alcohol Drinking↗
Association of hypertensive status and its drug treatment with lipid and haemostatic factors in middle-aged men: the PRIME study.
AIMS: To assess the association of hypertensive status and antihypertensive drug treatment with lipid and haemostatic levels in middle-aged men. METHODS AND RESULTS: Hypertensive status, antihypertensive drug treatment, total and high-density lipoprotein (HDL) cholesterol, triglyceride, apoproteins A-I and B, lipoparticles LpA-I, LpE:B and Lp(a), fibrinogen, plasminogen activator inhibitor-1 (PAI-1) activity and factor VII were assessed in a sample of men 50-59 years living in France (n = 7050) and Northern Ireland (n = 2374). After adjustment for age, body mass index, smoking status, educational level, country, alcohol drinking and hypolipidaemic drug treatment, untreated hypertensive subjects had higher levels of total cholesterol, triglyceride, apoproteins A-I and B and PAI-I activity than normotensive subjects. On univariate analysis, diuretics decreased total and HDL-cholesterol and apoproteins A-I and B; those differences remained after multivariate adjustment. Treatment with beta-blockers decreased total and HDL-cholesterol, apoprotein A-I and LpA-I, and this effect remained after multivariate adjustment. Calcium channel blockers decreased total cholesterol and apoproteins A-I and B; those differences remained significant after multivariate adjustment. ACE inhibitors decreased total cholesterol, triglycerides, apoprotein B and LpE:B; and this effect remained after multivariate adjustment. Analysis of the subjects on monotherapy showed beta-blockers to decrease total cholesterol and HDL parameters and angiotensin-converting enzyme (ACE) inhibitors to decrease low-density lipoprotein (LDL)-related parameters, while no effect was found for the other antihypertensive drugs. CONCLUSIONS: Hypertensive status is associated with an unfavourable lipid and haemostatic profile in middle-aged men. Antihypertensive treatment with beta-blockers decreases HDL parameters, whereas treatment with ACE inhibitors appears to decrease total cholesterol and LDL-related parameters.
Angiotensin-Converting Enzyme Inhibitors↗
Polymorphisms of the human matrix gla protein (MGP) gene, vascular calcification, and myocardial infarction.
The matrix Gla protein (MGP) is an important inhibitor of vessel and cartilage calcification that is strongly expressed in human calcified, atherosclerotic plaques and could modulate plaque calcification and coronary heart disease risk. Using a genetic approach, we explored this possibility by identifying polymorphisms of the MGP gene and testing their possible association with myocardial infarction (MI) and plaque calcification. Eight polymorphisms were identified in the coding and 5'-flanking sequences of the MGP gene. All polymorphisms were investigated in 607 patients with MI and 667 control subjects recruited into the ECTIM Study (Etude Cas-Témoins de l'Infarctus du Myocarde) and in 717 healthy individuals with echographically assessed arterial calcification and atherosclerosis who were participating in the AXA Study. In the ECTIM Study, alleles and genotypes were distributed similarly in patients and controls in the whole study group; in only 1 subgroup of subjects defined as being at low risk for MI were the concordant A-7 and Ala 83 alleles more frequent in patients with MI than in controls (P<0.003). In the AXA Study among subjects with femoral atherosclerosis, the same alleles were more common in the presence than the absence of plaque calcification (P<0.025). The other MGP polymorphisms were not associated with any investigated clinical phenotype. Transient transfection experiments with allelic promoter-reporter gene constructs and DNA-protein interaction assays were carried out to assess possible in vitro functionality of the promoter variants detected at positions -814, -138, and -7 relative to the start of transcription. When compared with the -138 T allele, the minor -138 C: allele consistently conferred a reduced promoter activity of -20% (P<0.0001) in rat vascular smooth muscle cells and of -50% (P<0.004) in a human fibroblast cell line, whereas the other polymorphisms, including -7, displayed no evidence of in vitro functionality. We conclude that the A-7 or Ala 83 alleles of the MGP gene may confer an increased risk of plaque calcification and MI; however, the observed relationships are weak or limited to subgroups of patients and therefore need confirmation.
Adolescent↗
Polymorphisms in the 5' regulatory region of the tissue factor gene and the risk of myocardial infarction and venous thromboembolism: the ECTIM and PATHROS studies. Etude Cas-Témoins de l'Infarctus du Myocarde. Paris Thrombosis case-control Study.
Tissue factor (TF) is a transmembrane protein considered to be responsible for the initiation of coagulation. TF gene expression may be induced in monocytes and endothelial cells and is present in atherosclerotic plaque to initiate thrombus formation. To investigate whether individual differences in TF gene expression could predispose subjects to thrombosis, we sequenced the 5' domain of the gene up to nucleotide 2732 and found 6 different polymorphisms: 4 of them were completely concordant and defined 2 haplotypes with similar frequencies, designated as 1208 D and 1208 I. Genotyping of patients with myocardial infarction in a case-control study involving 2354 subjects showed no association between the polymorphisms and nonfatal coronary thrombosis. In another study involving 255 patients with venous thromboembolism and 1204 controls, allele D was less common in the cases (P=0.022). The odds ratio associated with the presence of at least 1 D allele was 0.72 (P=0. 031). Comparison of subgroups of control subjects who were homozygous for the D or I allele demonstrated a lower plasma TF concentration in DD homozygotes. These results indicate that the TF gene promoter exists in 2 major forms differing at 4 sites. The 1208 D haplotype is not associated with coronary thrombosis but is associated with reduced plasma TF levels and a lower risk of venous thrombosis.
5' Untranslated Regions↗
Functional polymorphism in the regulatory region of gelatinase B gene in relation to severity of coronary atherosclerosis.
BACKGROUND: Gelatinase B, a matrix metalloproteinase that has proteolytic activity against connective tissue proteins, has been suggested to be important in the connective tissue remodeling processes associated with atherogenesis and plaque rupture. This study tested the hypothesis that sequence variation in the promoter region of the gelatinase B gene influences its expression, predisposing individuals carrying certain genetic variants to more severe atherosclerosis. METHODS AND RESULTS: Single-strand conformation polymorphism analysis was carried out to search the promoter region of the gene encoding gelatinase B for naturally occurring genetic variation. As a result, an unreported common polymorphism was detected, which arose from a cytosine (C) to thymidine (T) transition at position -1562 relative to the start of transcription. Transient transfection experiments and DNA-protein interaction assays indicated that the T allele had a higher promoter activity than the C allele, which appeared to be due to preferential binding of a putative transcription repressor protein to the C allelic promoter. A sample of 584 male patients with myocardial infarction and 645 age-matched male healthy control subjects were genotyped. The allele frequencies were not significantly different between the cases and control subjects. However, in 374 patients with available angiographic data, 26% of those carrying 1 or 2 copies of the T allele had >50% stenosis in 3 coronary arteries, whereas only 15% of C/C homozygotes had triple-vessel disease. CONCLUSIONS: These data suggest that this functional genetic variation influences gelatinase B gene promoter activity in an allele-specific manner and has an effect on atherosclerotic phenotype.
Adult↗