The Relationship Between Vascular Endothelial Growth Factor Cis- and Trans-Acting Genetic Variants and Metabolic Syndrome.

Background: We have investigated the association between 4 cis- and trans-genetic variants (rs6921438, rs4416670, rs6993770 and rs10738760) of the vascular endothelial growth factor (VEGF) gene and metabolic syndrome (MetS) and its individual components in an Iranian population.

Material & Method: Three hundred and thirty-six subjects were enrolled and MetS was defined according to the International-Diabetes-Federation (IDF) criteria. Genotyping was carried out in all the individuals for 4 VEGF genetic variants using an assay based on a combination of multiplex polymerase chain reaction and biochip array hybridization.

Genotype-phenotype associations in French patients with phenylketonuria and importance of genotype for full assessment of tetrahydrobiopterin responsiveness.

Background: Mutations in Phenylalanine Hydroxylase (PAH) gene cause phenylketonuria. Sapropterin (BH4), the enzyme cofactor, is an important therapeutical strategy in phenylketonuria. However, PAH is a highly polymorphic gene and it is difficult to identify BH4-responsive genotypes.

Genetic determined low response to thienopyridines is associated with higher systemic inflammation in smokers.

Aim: To investigate whether the interactions of CYP2C19*2 and CYP2C19*17 with smoking are associated with the levels of P2Y12 receptor inhibition and CRP, in on-thienopyridine post-stenting patients.

Methods & Results: At 1-month follow-up, the interactions of smoking and CYP2C19 polymorphisms on the vasodilator-stimulated phosphoprotein - platelet reactivity index (VASP PRI), and CRP were explored in three metabolizing groups (1128 patients) as follow: poor metabolizers (*2 carriers/*17 noncarriers); intermediate metabolizers (*2 carriers/*17 carriers or *2 noncarriers/*17 noncarriers); and ultrarapidmetabolizers (*2 allele noncarriers/*17 carriers). The interactions of metabolizing status and smoking was significant for CRP (p = 0.

Influence of genetic variations on levels of inflammatory markers of healthy subjects at baseline and one week after clopidogrel therapy; results of a preliminary study.

We aimed to assess the association between the most common polymorphisms of cytochrome P450 (CYP) epoxygenases on the plasma levels of inflammatory markers in a population of healthy subjects. We also sought to determine whether CYP2C19 2 polymorphism is associated with the anti-inflammatory response to clopidogrel. In a population of 49 healthy young males, the baseline plasma levels of inflammatory markers including C-reactive protein, haptoglobin, orosomucoid acid, CD-40 were compared in carriers vs.

Dairy product consumption, calcium intakes, and metabolic syndrome-related factors over 5 years in the STANISLAS study.

Objective: We assessed the associations of total dairy products; milk, yogurt, and cottage cheese; cheese; and calcium with 5-y changes in components of the metabolic syndrome.

Methods: Two hundred eighty-eight men and 300 women 28 to 60 y of age from the suivi temporaire annuel non invasif de la santé des lorrains assurés sociaux (STANISLAS) cohort completed at baseline a 3-d dietary record. Statistics were performed using multivariate regression analysis.

Alcohol Consumption, Beverage Preference, and Diet in Middle-Aged Men from the STANISLAS Study.

The question about differences in dietary patterns associated with beer, wine, and spirits is still unresolved. We used diet data from 423 middle-aged males of the STANISLAS Study. Using adjusted values for covariates, we observed a negative significant association between increasing alcohol intakes and the consumption of milk, yogurt, and fresh/uncured cheese, sugar and confectionery, vegetables and fruits, and a significant positive relationship with cheese, meat and organs, pork-butcher's meat, and potatoes.

Clinical necessity of partitioning of human plasma haptoglobin reference intervals by recently-discovered rs2000999.

Background: Very recently, we identified a novel polymorphism, rs2000999, located in haptoglobin gene (HP) as a strong genetic determinant of the haptoglobin levels (Hp). We aim to determine the reference values of Hp on the basis of its main sources of biological variation including the rs2000999 in a large French origin population, the STANISLAS Family Study (SFS).

Methods: Through a stepwise regression analysis, the main biological variables of Hp levels were identified in 3129 "apparently" disease-free individuals of the SFS.

A genome-wide association study identifies rs2000999 as a strong genetic determinant of circulating haptoglobin levels.

Haptoglobin is an acute phase inflammatory marker. Its main function is to bind hemoglobin released from erythrocytes to aid its elimination, and thereby haptoglobin prevents the generation of reactive oxygen species in the blood. Haptoglobin levels have been repeatedly associated with a variety of inflammation-linked infectious and non-infectious diseases, including malaria, tuberculosis, human immunodeficiency virus, hepatitis C, diabetes, carotid atherosclerosis, and acute myocardial infarction.

High prevalence of metabolic syndrome in Iran in comparison with France: what are the components that explain this?

Background: The aim of this study was to investigate the difference in the prevalence of metabolic syndrome and its components between an Iranian and a French population.

Methods: The prevalence of metabolic syndrome, defined according to the Adult Treatment Panel III (ATP III), and of related abnormalities, was estimated in 1,386 French and 1,194 Iranian adults.

Results: The prevalence of metabolic syndrome was significantly higher in Iranian women (55.

Klotho KL-VS genotype is involved in blood pressure regulation.

Background And Aims: Genome-wide linkage analysis studies reported the importance of the long arm of chromosome 13 in systolic blood pressure regulation. Therefore, isolating a genetic variant related to this chromosomal region could be challenging. Klotho KL-VS allele is located on this chromosomal region and its relationships with cardio-vascular risk factors need extensive investigations.

Biological and genetic factors associated with ABCB1 and pregnane-X-receptor expressions in peripheral blood mononuclear cells in the STANISLAS cohort.

Background: ABCB1 is a membrane transporter ubiquitously expressed particularly in peripheral blood mononuclear cells (PBMCs). Resistance to drugs is associated with genetic variations of its gene and with modulation of its expression through the pregnane-X-receptor (PXR) transcription factor. We have previously shown that ABCB1 polymorphisms were associated with blood lipid concentrations.

Human formyl peptide receptor 1 C32T SNP interacts with age and is associated with blood pressure levels.

Background: Human formyl peptide receptor 1 (FPR1) mediates inflammatory responses, recognized as important participants in the physiopathology of hypertension. Similarly, FPR1 C32T SNP is associated with inflammation and BP related pathways. Therefore, the relationship between FPR1 C32T SNP, BP and hypertension needs to be investigated.

Metabolic syndrome-related composite factors over 5 years in the STANISLAS family study: genetic heritability and common environmental influences.

Background: We estimated genetic heritability and common environmental influences for various traits related to metabolic syndrome in young families from France.

Methods: At entrance and after 5 years, nineteen traits related to metabolic syndrome were measured in a sample of families drawn from the STANISLAS study. In addition, 5 aggregates of these traits were identified using factor analysis.

Human formyl peptide receptor 1 (FPR1) c.32C>T SNP is associated with decreased soluble E-selectin levels.

Aims: The human formyl peptide receptor (FPR) is a G protein-coupled chemoattractant receptor that is thought to mediate inflammatory responses. The FPR1 gene is highly polymorphic. In a recent study, the FPR1 c.

Sex-dependent associations of leptin with metabolic syndrome-related variables: the Stanislas study.

Serum leptin has been reported to be associated in a sex-dependent manner with C-reactive protein (CRP), independently of adiposity. We tested the hypothesis that leptin is associated, independently of anthropometry indexes and in a sex-dependent way, with other inflammatory markers and variables related to metabolic syndrome (MS). In 384 healthy middle-aged adults (192 men and 192 women) total fat mass (FM), waist circumference (WC), serum leptin and 15 MS-related parameters (systolic and diastolic blood pressure, triglycerides, cholesterol, high density lipoprotein (HDL)-cholesterol, apo AI and B, fasting glucose, uric acid, CRP, orosomucoid and haptoglobin levels and aspartate aminotransferase (ASAT), alanine aminotransferase (ALAT) and gamma-glutamyl transferase (GGT) activities) were measured.

Association between EGF and lipid concentrations: a benefit role in the atherosclerotic process?

Context And Objective: Previous in vitro studies have shown a relationship between epidermal growth factor (EGF) and lipid metabolism. Indeed, EGF is able to modulate lipoprotein fractions in human fetal intestine and hepatic-derived cell lines. The aim of this study was to search for potential associations between EGF concentrations and lipid parameters in both plasma and peripheral blood mononuclear cells (PBMCs) among healthy individuals.

Nutritional and genetic determinants of vitamin B and homocysteine metabolisms in neural tube defects: a multicenter case-control study.

Neural tube defects (NTDs) are severe congenital malformations due to failure of neural tube formation in early pregnancy. The proof that folic acid prevents NTDs raises the question of whether other parts of homocysteine (Hcy) metabolism may affect rates of NTDs. This French case-control study covered: 77 women aged 17-42 years sampled prior to elective abortion for a severe NTDs (cases) and 61 women aged 20-43 years with a normal pregnancy.

The lipoprotein lipase serine 447 stop polymorphism is associated with altered serum carotenoid concentrations in the Stanislas Family Study.

Background: Carotenoids are mainly carried by lipoproteins in blood, however little is known about the influence of polymorphisms of apolipoproteins (apo), cholesterol ester transfer protein (CETP) and lipoprotein lipase (LPL) involved in serum lipid metabolism.

Objective: We aimed to analyze whether serum concentrations of 5 carotenoids (lutein-zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, beta-carotene) are associated with common polymorphisms of Apo E, Apo B, Apo CIII, CETP, and LPL.

Methods: Serum concentrations of lutein-zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, and beta-carotene were measured and polymorphisms of Apo E (cys112arg and arg158cys), Apo B (thr71ile), Apo CIII [C(-482)T, Apo CIII T(-455)C, Apo CIII C1100T, Apo CIII C3175G, Apo CIII T3206G], CETP (ile405val), and LPL (S447X) were determined in a sample of 447 children and adults drawn from the Stanislas Study.

Association of classical and related inflammatory markers with high-sensitivity C-reactive protein in healthy individuals: results from the Stanislas cohort.

Background: Although high-sensitivity C-reactive protein (hs-CRP) has emerged as a cardiovascular marker, questions arise regarding the relative information provided by other inflammatory molecules. Therefore, as a first step, we examined interrelationships between serum hs-CRP concentrations and inflammatory, adhesion and growth factors in healthy adults.

Methods: Circulating concentrations of hs-CRP, haptoglobin, orosomucoid, interleukin-6 (IL-6), IL-8, IL-18, tumor necrosis factor-alpha (TNF-alpha), TNF-receptor II (TNF-RII), E-, P-, and L-selectins, intercellular adhesion molecule-1 (ICAM-1), monocyte chemoattractant protein-1, endothelial growth factor (EGF), vascular EGF (VEGF), insulin-like growth factor-1 (IGF-1) and IGF-binding protein (IGFBP-3) were measured in 154 men and 161 women of the Stanislas cohort.

[Preanalytical variations of proteic biomarkers].

In the area of proteomic, results of analysis were for a long time dependant on analytical variations. Nowadays, due to the emergence of new technologies and controls of data, these variations are less important than those due to preanalytical conditions, which are difficult to overcome. The reasons are due to the number of parameters and to the fact that the biologist is not always fully informed.

Heritability for plasma VEGF concentration in the Stanislas family study.

Vascular endothelial growth factor (VEGF), a key regulator of blood vessel function during angiogenesis, has been related to various diseases including atherosclerosis, neurodegenerative disorders and cancers. However, data about genetic determinants of its concentration in blood are scarce. The present study aimed at estimating additive genetic heritability, household component effect and the influence of 3 common VEGF polymorphisms on plasma VEGF concentration.

Environmental influence on the worldwide prevalence of a 776C->G variant in the transcobalamin gene (TCN2).

Background: A 776C-->G variant (dbSNP ID: rs1801198) in the transcobalamin gene (TCN2; MIM# 275350) decreases the cellular and plasma concentration of transcobalamin and thereby influences the cellular availability of vitamin B(12).

Objective: To evaluate the worldwide prevalence of this variant and its association with homocysteine plasma level.

Methods: The study was performed in 1433 apparently healthy subjects, including Afro-Americans and Afro-Africans and in 251 Afro-Africans participants with severe malaria.

Genetic and environmental contributions to serum ascorbic acid concentrations: the Stanislas Family Study.

Although numerous environmental factors are documented to influence serum ascorbic concentrations, little is known about the genetic versus environmental contributions to variation of this trait. The aim of this study was to estimate family correlation and, additive genetic heritability and household effects in a variance component analysis for serum ascorbic acid concentrations. In a sample of ninety French families, information was obtained regarding serum ascorbic acid concentrations, usual dietary intake, lifestyle, and other related covariates.

Association between TNF and IL-1 bloc polymorphisms and plasma MCP-1 concentration.

Background: Circulating MCP-1 concentration was found to be increased in cardiovascular diseases and is of high interest in the list of biomarkers of atherosclerosis. TNF-alpha, LT-alpha, IL-1alpha and IL-1beta are four proinflammatory cytokines that regulate MCP-1 concentration in vitro. We hypothesized that specific genetic polymorphisms in TNF, LTA, IL-1A and IL-1B genes could modulate plasma MCP-1 concentration.