Concordance of two multiple analytical approaches demonstrate that interaction between BMI and ADIPOQ haplotypes is a determinant of LDL cholesterol in a general French population.

Genetic and environmental factors are involved in insulin resistance (IR). IR and dyslipidemia associate with increased risk of cardiovascular diseases. Plasma low-density lipoprotein cholesterol (LDL-C) level is a marker of cardiovascular risk.

An age effect on the association of common variants of ACE with Alzheimer's disease.

It is now well established that vascular risk factors are associated with cognitive performances. The renin-angiotensin system (RAS) components, major determinants of the cardiovascular system, are expressed in the brain and were shown to play a role on amyloid metabolism, learning and memory. The angiotensin-converting enzyme (ACE), a pivotal RAS protein, is encoded by a huge gene containing many variants, one of them, the I/D variant (rs1799752), being associated with Alzheimer's disease (AD).

Haplotypes across ACE and the risk of Alzheimer's disease: the three-city study.

The purpose of this study was to examine the impact of two polymorphisms (rs4291A>T and rs4343G>A) in the ACE gene on the risk of Alzheimer's disease (AD), using a population-based cohort of 9294 subjects selected from the electoral rolls of three French cities (the Three-City Study). Two follow-up examinations took place 2 and 4 years after inclusion. Diagnosis of dementia was assessed at baseline and at each follow-up examination by neurologists independent of the 3C Study group.

An apolipoprotein A-I gene promoter polymorphism associated with cognitive decline, but not with Alzheimer's disease.

Background/aims: Accumulating biological and epidemiological evidence suggests a close link between cholesterol metabolism and the pathophysiology of Alzheimer's disease (AD). The observation that the use of statins reduces the risk of AD sustains this hypothesis. Apolipoprotein A-I (APOA1) is the major component of the high-density lipoproteins, particles involved in reverse cholesterol transport.

Low-density lipoprotein receptor-related protein 8 gene polymorphisms and dementia.

The sole known genetic risk factor for sporadic Alzheimer's disease (AD) is the gene encoding apolipoprotein E (APOE), but the underlying mechanism is still under debate. One hypothesis relies on an interaction between APOE and its receptors. Previous studies have shown association of LDL receptor-related protein (LRP1) with AD and we previously reported a modulation by LRP1 of the risk of AD conferred by the -499A>G promoter polymorphism of the MAPK8IP1, a gene encoding Islet-brain-1 (IB1), the human counterpart of c-Jun NH(2) terminal kinase interacting protein-1 (JIP-1).

A prospective evaluation of left ventricular remodeling after inaugural anterior myocardial infarction as a function of gene polymorphisms in the renin-angiotensin-aldosterone, adrenergic, and metalloproteinase systems.

Background: Left ventricular remodeling (LVR) is a strong predictor of cardiovascular events after myocardial infarction (MI). Although several factors have been shown to influence LVR, interindividual variability exists. Some studies have suggested that gene polymorphisms may be associated with LVR, but these studies were limited by either a retrospective design or the inclusion of limited patient numbers.

Impact of a CART promoter genetic variation on plasma lipid profile in a general population.

The cocaine and amphetamine regulated transcript (CART), an anorexigenic peptide responding to leptin, is expressed in various areas of the hypothalamus. The role of CART in humans and its potential contribution to abnormalities in feeding control are mostly unknown. Since CART plays an important role in the hypothalamic regulation of energy balance by reducing food intake and increasing lipid substrate utilization, it might affect cholesterol metabolism as Neuropeptide Y or pro-opiomelanocortin do.

The impact of the AMPD1 gene polymorphism on exercise capacity, other prognostic parameters, and survival in patients with stable congestive heart failure: a study in 686 consecutive patients.

Background: Previous studies have demonstrated that the adenosine monophosphate deaminase 1 (AMPD1) C34T polymorphism may be associated with survival in cardiac populations with a protective effect of the T allele. However, these studies included limited number of patients with few cardiovascular events.

Methods: We prospectively analyzed the impact of the C34T polymorphism of the AMPD1 gene in 686 unrelated white patients with stable congestive heart failure related to left ventricular systolic dysfunction.

Impact of the matrix metalloproteinase MMP-3 on dementia.

Cerebral accumulation of beta-amyloid peptide (Abeta) is a central event in the pathogenesis of Alzheimer's disease (AD). Several proteases were shown to hydrolyze Abeta in vitro or in cell-based assays, and are likely candidates for a role in Abeta clearance in brain. Previous reports suggest that matrix metalloproteinases (MMPs) could be involved in such a mechanism.

Impact of APOA5/A4/C3 genetic polymorphisms on lipid variables and cardiovascular disease risk in French men.

Objective: The goal of the present study was to assess the impact of 4 single nucleotide polymorphisms (SNPs) of APOA5/A4/C3 gene cluster on lipid levels and coronary heart disease (CHD) risk in French men.

Methods: A total of 442 men with CHD were recruited from the university hospital and compared to 475 men free of CHD from the population of the same geographical area. The APOA5 S19W, APOA5 -l2,238T>C, APOA4 T347S and APOC3 -482C>T SNPs were examined.

The impact of beta-adrenoreceptor gene polymorphisms on survival in patients with congestive heart failure.

Objective: Discordant results have been published regarding a possible association between beta-adrenoreceptor (betaAR) gene polymorphisms and survival in patients with congestive heart failure (CHF). The aim of the study was to analyze the impact of five functional betaAR gene polymorphisms in patients with stable CHF.

Methods: We prospectively studied 444 consecutive patients with CHF related to left ventricular systolic dysfunction.

A common variant of endothelial nitric oxide synthase (Glu298Asp) is associated with collateral development in patients with chronic coronary occlusions.

Background: Experimental studies support an important role for endothelial nitric oxide synthase (eNOS) in the regulation of angiogenesis. In humans, a common polymorphism exists in the eNOS gene that results in the conversion of glutamate to aspartate for codon 298. In vitro and in vivo studies have suggested a decreased NOS activity in patients with the Asp298 variant.

Study of a new PPARgamma2 promoter polymorphism and haplotype analysis in a French population.

Peroxisome proliferator-activated receptor-gamma (PPARgamma) plays a role in adipocyte differentiation and insulin sensitization. We identified and characterized a new C/T substitution at position -689 (-689C>T) in the P2 promoter of PPARgamma in a putative GATA binding site. By electrophoretic mobility shift assay, both GATA2 and GATA3 proteins could bind weakly to the wild-type P2 -689 GATA binding site but not to the mutated site.

Association between beta-1 and beta-2 adrenergic receptor gene polymorphisms and the response to beta-blockade in patients with stable congestive heart failure.

Previous studies have clearly demonstrated the beneficial effect of beta-blockers in patients with stable congestive heart failure (CHF). beta-blockers improve left ventricular ejection fraction (LVEF) and reduce cardiac mortality. However, there is an interindividual variability in the response to these agents.

Analysis of sequence variability in the CART gene in relation to obesity in a Caucasian population.

Background: Cocaine and amphetamine regulated transcript (CART) is an anorectic neuropeptide located principally in hypothalamus. CART has been shown to be involved in control of feeding behavior, but a direct relationship with obesity has not been established. The aim of this study was to evaluate the effect of polymorphisms within the CART gene with regards to a possible association with obesity in a Caucasian population.

Role of transcription factor KLF11 and its diabetes-associated gene variants in pancreatic beta cell function.

KLF11 (TIEG2) is a pancreas-enriched transcription factor that has elicited significant attention because of its role as negative regulator of exocrine cell growth in vitro and in vivo. However, its functional role in the endocrine pancreas remains to be established. Here, we report, for the first time, to our knowledge, the characterization of KLF11 as a glucose-inducible regulator of the insulin gene.

APOE promoter polymorphisms and dementia in the elderly.

Previous observations suggest a contribution of two APOE promoter polymorphisms (-219 G/T and -491 A/T) in dementia. From two independent populations of elderly (mean age of 84 and 85 years old, respectively), we observed that subjects bearing the -219T allele were at increased risk of dementia (OR = 1.9 (95% CI, 1.

Prognostic impact of matrix metalloproteinase gene polymorphisms in patients with heart failure according to the aetiology of left ventricular systolic dysfunction.

Aims: To assess the possible effect of functional polymorphisms in matrix metalloproteinase (MMP) gene promoters on the clinical outcome of patients with heart failure.

Methods And Results: We studied 444 consecutive patients who were referred to our centre for evaluation of left ventricular dysfunction. We extracted genomic DNA from white blood cells and determined the -1306 C >T MMP-2, -1171 5A > 6A MMP-3, and -1562 C >T MMP-9 polymorphisms.

Commonalities between genetics of cardiovascular disease and neurodegenerative disorders.

Purpose Of Review: Numerous epidemiological and clinical data suggest that neurodegenerative disorders, such as Alzheimer's disease, may be related directly or indirectly to cardiovascular risk. Genetic studies have demonstrated that they share at least one common susceptibility gene, encoding apolipoprotein E, a modulator of cardiac risk and of cognitive impairment. Several studies have suggested that other genes involved in the development of cardiovascular diseases may be involved.

Paraoxonase 1 gene polymorphisms and dementia in humans.

Several clinical and epidemiological studies suggest that Alzheimer's disease (AD) and vascular dementia share common risk factors. Oxidative stress is one of these well recognized factors. It can result from an excess of free-radical activity and impaired antioxidant defenses.

Beta-adrenergic receptor blockade and the angiotensin-converting enzyme deletion polymorphism in patients with chronic heart failure.

Background: Beta-adrenergic receptor blockade is an established treatment of chronic heart failure (HF). Previous studies have suggested a potential pharmacogenetic interaction between beta-blocker therapy and the angiotensin-converting enzyme (ACE) I/D polymorphism in patients with HF.

Aims: We designed this study to analyze changes in myocardial function of HF patients in response to beta-blocker therapy as a function of the ACE I/D polymorphism.

The Gly16-->Arg16 and Gln27-->Glu27 polymorphisms of beta2-adrenergic receptor are associated with metabolic syndrome in men.

Endogenous catecholamines contribute to regulation of adipose tissue lipolysis, glucose homeostasis, and vascular tone. The goal of the present study was to assess the association between the Gly(16)-->Arg(16) and Gln(27)-->Glu(27) polymorphisms of the beta(2)-adrenergic receptor and metabolic syndrome. Participants were recruited in a population survey and included 1195 men and women.