Thierry Brousseau

Early effect of ApoE-ϵ4 allele on cognitive results in a group of highly performing subjects: the EVA study ☆

Abstract We examined the association between apolipoprotein E (ApoE) ϵ4 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 ϵ4 alleles was 70.6%, 21.4% and 1.9%, respectively. The ϵ4 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-ϵ4 allele is early associated with low normal cognitive performances in areas which are not specifically affected at the subclinical onset of dementia.

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.

Association of arginase 1 gene polymorphisms with the risk of myocardial infarction and common carotid intima-media thickness

Background: Recently, it was suggested that arginase (ARG)1 plays an important role in atherogenesis. However, because of its complex functions depending on vascular cell type, its impact on atherogenesis remains unclear. Objective: To evaluate the association between ARG1 polymorphisms and phenotypes related to atherosclerosis. Methods: Among 10 ARG1 polymorphisms selected from databases, 4 single-nucleotide polymorphisms (rs2781666; rs2781667; rs2781668; rs17599586) were tested for association with myocardial infarction (MI) in a case–control study (350 cases vs 581 controls), and with common carotid artery (CCA) intima–media thickness (CCA-IMT) in an independent sample of 963 subjects (Etude du Vieillissement Artériel (EVA) study). Results: The genotype distribution of the rs2781666 G/T polymorphism differed significantly between MI cases and controls (p = 0.005), and the risk of MI was consistently increased for both GT heterozygotes (OR (95% CI) 1.5 (1.1 to 2.0)) and TT homozygotes (OR (95% CI) 2.2 (1.1 to 4.4)). In the EVA study, the rs2781666 polymorphism was also associated with an increase in CCA-IMT (p = 0.010), a surrogate marker of MI. Conclusions: The ARG1 rs2781666 polymorphism was consistently associated with MI and an increased CCA-IMT. These findings reinforce the hypothesis of a significant role of ARG1 in vascular pathophysiology.

Familial defective apolipoprotein B-100 and myocardial infarction. The ECTIM study

“INSERM U325, Institut Pasteur de Lille, I rue du Professeur Calmette, BP245, 59019 Lille Cedex, France bMONICA-Bas-Rhin, Laboratoire d’Epidemiologie et de Sante Publique, I I rue Humann, 67085 Strasbourg Cedex, France “.MONICA Haute-Garonne, INSERM V326-ORS, Place du Docteur Baylac, 31059 Toulouse Cedex, France dBeljast MONIC.4 Project, Department of Epidemiology and Public Health, The Queen’s University of Be&t, Grosvenor Road, Belfast BT12 6BJ, Northern Ireland, UK “INSERM SC7, 17 rue du Fer ri Moulin, 75005 Paris, France ‘MONICA-Lille, Institut Pasteur de Lille, I rue du Projesseur Calmette, BP245, 59019 Liile, France

Association of OAZ1 Gene Polymorphisms With Subclinical and Clinical Vascular Events

Objective— Proliferation and migration of vascular smooth muscle cells (VSMCs) are striking features shared by vascular ageing, atherosclerosis, and in-stent restenosis. VSMC biology depends in part on polyamines whose metabolism is closely regulated by ornithine decarboxylase antizyme 1 (OAZ1). Therefore, we sought for association between OAZ1 gene polymorphisms and various outcomes involving VSMC proliferation. Methods and Results— Systematic screening of the OAZ1 gene enabled to detect 21 variants. The impact of 4 selected tag polymorphisms (+849C/T, +851G/T, +1804G/A, and +2222A/G) was evaluated in 3 independent association studies. In a sample of 205 patients, the +2222G allele was associated with an increased risk of 6-month coronary in-stent restenosis (OR [95%CI]=2.1 [1.2 to 3.6]; P=0.0071). In a sample of 1001 subjects participating to the EVA study, the +2222G allele was longitudinally associated with a 4-year increase in common carotid intima-media thickness (P=0.047). In a case-control study (466 cases versus 466 controls), the risk of coronary heart disease associated with the +2222G allele was 1.3 (95%CI=[1.1 to 1.6]; P=0.026). No other significant association was consistently detected. Conclusions— We identified the OAZ1+2222A/G polymorphism as a potential genetic marker of vascular events. Our findings strengthen the hypothesis that the polyamine metabolism plays a role in vascular diseases.

Association of Ornithine Transcarbamylase Gene Polymorphisms With Hypertension and Coronary Artery Vasomotion

BACKGROUND Previous studies have suggested that the activity of enzymes involved in the urea cycle may modulate nitric oxide (NO) production, arterial vasomotion, and hypertension. Our aim was to determine whether hypertension and coronary vasomotion could be associated with polymorphisms within the ornithine transcarbamylase (OTC) gene, located on chromosome X and coding for a key-enzyme of the urea cycle. METHODS Among 11 OTC polymorphisms that were originally selected from databases, the tag single-nucleotide polymorphism (SNP) rs5963409 and the independent SNP rs1800321 were tested for association with hypertension in two independent population samples recruited in Northern (Multinational MONItoring of trends and determinants in CArdiovascular disease (MONICA) study, n = 1,138) and Western (Etude du Vieillissement Artériel (EVA) study, n = 1,166) France. The vasomotor response of coronary arteries to methylergonovine maleate and isosorbide dinitrate was also evaluated in an independent sample (the vasomotion study, n = 121). RESULTS In males, the frequency of the rs5963409 minor allele was consistently higher in hypertensive (HT) than in normotensive subjects in the MONICA and EVA studies. In the combined sample, the rs5963409 minor allele was associated with an increased risk of hypertension (odds ratio (OR) (95% confidence interval (CI)) = 1.45 (1.10-1.90); P = 0.008). This association was independent of classical confounding factors. Consistently, rs5963409 minor allele was associated with a greater susceptibility to vasoconstriction in response to methylergonovine maleate (P = 0.0072). In contrast, no significant association between rs5963409 and hypertension could be detected in females. CONCLUSION Our results suggest that the OTC rs5963409 polymorphism may be associated with hypertension and coronary vasomotion in males.

A study on the polymorphisms of the renin–angiotensin system pathway genes for their effect on blood pressure levels in males from Algeria

Introduction Several studies have assessed the relationship between blood pressure (BP) and polymorphisms within the genes encoding angiotensinogen (AGT), angiotensin II type 1 receptor (AT1R) and angiotensin-converting enzyme (ACE). However, considering the relatively large discrepancy in frequency and impact of these variants between ethnic groups and populations, still unavailable data from Algerian population are needed. Objective Our purpose is to evaluate the association between the AGT M235T, AT1R +1166A/C and ACE I/D polymorphisms and variations in systolic (SBP), diastolic (DBP) and pulse pressure (PP) values. Methods The associations with BP were assessed in a representative sample of 115 male subjects free of coronary heart disease (CHD). The AGT M235T, AT1R +1166A/C and ACE I/D polymorphisms were determined by PCR-ASO and PCR-RFLP analysis, respectively. Results We showed no associations between the AGT M235T, AT1R +1166A/C nor the ACE I/D polymorphisms with variations in BP values. However, concerning the ACE I/D polymorphism, subjects carrying the ACE I allele tended to have higher SBP (+4.1 mmHg) and PP values (+3.2 mmHg) than DD subjects (adjusted p = 0.087 and p = 0.102, respectively). Conclusion The ACE I/D polymorphism needs further investigation in a larger Algerian study, especially concerning its putative impact on SBP and PP.