Characterization of a Human Point Mutation of VGLUT3 (p.A211V) in the Rodent Brain Suggests a Nonuniform Distribution of the Transporter in Synaptic Vesicles.

The atypical vesicular glutamate transporter type 3 (VGLUT3) is expressed by subpopulations of neurons using acetylcholine, GABA, or serotonin as neurotransmitters. In addition, VGLUT3 is expressed in the inner hair cells of the auditory system. A mutation (p.

Design, synthesis and biological evaluation of small-azo-dyes as potent Vesicular Glutamate Transporters inhibitors.

Vesicular Glutamate Transporters (VGLUTs) allow the loading of presynapic glutamate vesicles and thus play a critical role in glutamatergic synaptic transmission. VGLUTs have proved to be involved in several major neuropathologies and directly correlated to clinical dementia in Alzheimer and Parkinson's disease. Accordingly VGLUT represent a key biological target or biomarker for neuropathology treatment or diagnostic.

In vivo imaging of intersynaptic vesicle exchange using VGLUT1 Venus knock-in mice.

The vesicular glutamate transporter VGLUT1 loads synaptic vesicles with the neurotransmitter glutamate and thereby determines glutamate release at many synapses in the mammalian brain. Due to its function and selective localization, VGLUT1 is one of the most specific markers for glutamatergic synaptic vesicles. It has been used widely to identify glutamatergic synapses, and its expression levels are tightly correlated with changes in quantal size, modulations of synaptic plasticity, and corresponding behaviors.

Optimal waist:height ratio cut-off point for cardiometabolic risk factors in Turkish adults.

Objective: To identify the optimal waist:height ratio (WHtR) cut-off point that discriminates cardiometabolic risk factors in Turkish adults.

Design: Cross-sectional study. Hypertension, dyslipidaemia, diabetes, metabolic syndrome score >or=2 (presence of two or more metabolic syndrome components except for waist circumference) and at least one risk factor (diabetes, hypertension or dyslipidaemia) were categorical outcome variables.

Comparison between Turkish Cardiovascular Risk Platform and United States National Cholesterol Education Program Adult Treatment Panel III definitions of the metabolic syndrome in Turkish adults.

The Turkish Cardiovascular Risk Platform (TCRP) calls for the diagnosis of the metabolic syndrome (MS) if insulin resistance, impaired fasting glucose, impaired glucose tolerance, or diabetes mellitus and >or=2 other established criteria are present. TCRP defines insulin resistance as a homeostasis model assessment >2.7.

Genome-wide linkage and association analyses to identify genes influencing adiponectin levels: the GEMS Study.

Adiponectin has a variety of metabolic effects on obesity, insulin sensitivity, and atherosclerosis. To identify genes influencing variation in plasma adiponectin levels, we performed genome-wide linkage and association scans of adiponectin in two cohorts of subjects recruited in the Genetic Epidemiology of Metabolic Syndrome Study. The genome-wide linkage scan was conducted in families of Turkish and southern European (TSE, n = 789) and Northern and Western European (NWE, N = 2,280) origin.

Impairment of SLC17A8 encoding vesicular glutamate transporter-3, VGLUT3, underlies nonsyndromic deafness DFNA25 and inner hair cell dysfunction in null mice.

Autosomal-dominant sensorineural hearing loss is genetically heterogeneous, with a phenotype closely resembling presbycusis, the most common sensory defect associated with aging in humans. We have identified SLC17A8, which encodes the vesicular glutamate transporter-3 (VGLUT3), as the gene responsible for DFNA25, an autosomal-dominant form of progressive, high-frequency nonsyndromic deafness. In two unrelated families, a heterozygous missense mutation, c.

Anthropometric indices and their relationship with cardiometabolic risk factors in a sample of Turkish adults.

Objective: To identify the best anthropometric index that predicts cardiometabolic risk factors.Design and settingCross-sectional study in Turkey, in 2003.

Subjects: Turkish men and women aged 18 years and over (n 1692) were examined.

Analysis of agreement among definitions of metabolic syndrome in nondiabetic Turkish adults: a methodological study.

Background: We aimed to explore the agreement among World Health Organization (WHO), European Group for the Study of Insulin Resistance (EGIR), National Cholesterol Education Program (NCEP), American College of Endocrinology (ACE), and International Diabetes Federation (IDF) definitions of the metabolic syndrome.

Methods: 1568 subjects (532 men, 1036 women, mean age 45 and standard deviation (SD) 13 years) were evaluated in this cross-sectional, methodological study. Cardiometabolic risk factors were determined.

Genetic and phenotypic architecture of metabolic syndrome-associated components in dyslipidemic and normolipidemic subjects: the GEMS Study.

Atherogenic dyslipidemia, manifest by low HDL-cholesterol and high TG levels, is an important component of ATP-III defined metabolic syndrome. Here, we dissected the phenotypic and genetic architecture of these traits by assessing their relationships with other metabolically relevant measures, including plasma adipo-cytokines, highly sensitive C-reactive protein (hsCRP) and LDL particle size, in a large family data set (n=2800) and in an independent set of dyslipidemic cases (n=716) and normolipidemic controls (n=1073). We explored the relationships among these phenotypes using variable clustering and then estimated their genetic heritabilities and cross-trait correlations.

Serum insulin and inflammatory markers in overweight individuals with and without dyslipidemia.

Context: The worldwide epidemic of overweight and obesity is setting the scene for a new wave of premature cardiovascular disease.

Objective: The objective of this study was to define relationships between dyslipidemia and other metabolic abnormalities in overweight subjects.

Design: This study included comparison of overweight subjects with and without dyslipidemia.

Hypertriglyceridemia: management of atherogenic dyslipidemia.

Elevated triglycerides are now considered an independent risk factor for coronary heart disease and continue to be a major risk for acute pancreatitis, especially when levels exceed 1000 mg/dL (SOR: B). Elevated triglycerides are a component of atherogenic dyslipidemia and often signal the presence of other conditions (eg, metabolic syndrome, type 2 diabetes mellitus) associated with an increased cardiovascular risk (SOR: A). When evaluating a patient with elevated triglycerides, it is important to be cognizant of all atherogenic lipoproteins to more accurately determine the risk of coronary heart disease (SOR: C).

Modulation of high-density lipoproteins in a population in istanbul, Turkey, with low levels of high-density lipoproteins.

The extent to which high-density lipoprotein (HDL) cholesterol levels can be increased in patients with low HDL cholesterol is important because low HDL cholesterol levels increase the risk of coronary heart disease (CHD). During the past 14 years, we have assessed risk factors in Turks, a population in which extremely low HDL cholesterol levels (mean 36 mg/dl in men, 42 mg/dl in women) are a prime CHD risk factor. Although genetically determined to a significant extent, these low HDL cholesterol levels can be modulated by lifestyle factors, as in other populations.

Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemia.

We conducted a genome-wide scan using variance components linkage analysis to localize quantitative-trait loci (QTLs) influencing triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol, and total cholesterol (TC) levels in 3,071 subjects from 459 families with atherogenic dyslipidemia. The most significant evidence for linkage to TG levels was found in a subset of Turkish families at 11q22 [logarithm of the odds ratio (LOD)=3.34] and at 17q12 (LOD=3.

Relation between atherogenic dyslipidemia and the Adult Treatment Program-III definition of metabolic syndrome (Genetic Epidemiology of Metabolic Syndrome Project).

Genetic Epidemiology of Metabolic Syndrome is a multinational, family-based study to explore the genetic basis of the metabolic syndrome. Atherogenic dyslipidemia (defined as low plasma high-density lipoprotein cholesterol with elevated triglycerides (<25th and >75th percentile for age, gender, and country, respectively) identified affected subjects for the metabolic syndrome. This report examines the frequency at which atherogenic dyslipidemia predicts the metabolic syndrome of the National Cholesterol Education Program Adult Treatment Panel III (ATP-III).

Risk determination of dyslipidemia in populations characterized by low levels of high-density lipoprotein cholesterol.

Background: Current guidelines for managing dyslipidemia qualify patients for treatment based on low-density lipoprotein cholesterol (LDL-C) levels and other risk factors for coronary heart disease (CHD). However, when LDL-C is the sole lipid criterion for initiating therapy, patients with levels below the treatment initiation threshold who are at high risk because of low levels (<40 mg/dL) of high-density lipoprotein cholesterol (HDL-C) might not be identified. Twenty percent of male patients with CHD in the United States fall into this category.

Managing dyslipidemia in Turkey: suggested guidelines for a population characterized by low levels of high density lipoprotein cholesterol.

Based on data from the Turkish Society of Cardiology and others, it is established that Turks have a high prevalence of coronary heart disease (CHD). Several risk factors are prominent in Turks: dyslipidemia, cigarette smoking, and hypertension. The dyslipidemia is unique in that very low levels of HDL-C and typically "normal" LDL-C levels characterize the Turkish population.

Sources of variability in genetic association studies: insights from the analysis of hepatic lipase (LIPC).

Genetic association studies have been widely used to identify loci that influence plasma lipoprotein concentrations, but few of the associations reported have proved consistently reproducible across different study populations. This lack of consistency is a widely recognized limitation of association studies, and is often ascribed to inadequate statistical power, population substructure, and population-specific linkage disequilibrium. However, few studies have assessed the causes of variability underlying a given genotype-phenotype association.

Plasma lipids in Turkish children: impact of puberty, socioeconomic status, and nutrition on plasma cholesterol and HDL.

In Turkish adults, HDL cholesterol (HDL-C) levels are 10-15 mg/dl lower than those of adults in western Europe and the United States. In this study, we determined whether HDL-C levels in Turks are low from birth to adulthood and assessed the effect of socioeconomic status (SES) on plasma lipids and lipoproteins. Analyses of cord blood from 105 Turkish newborns showed low levels of plasma cholesterol ( approximately 60 mg/dl) and HDL-C (approximately 30 mg/dl), consistent with results from other Western ethnic groups.

Low levels of high density lipoproteins in Turks, a population with elevated hepatic lipase. High density lipoprotein characterization and gender-specific effects of apolipoprotein e genotype.

Turks have strikingly low levels of high density lipoprotein cholesterol (HDL-C) (10-15 mg/dL lower than those of Americans or Western Europeans) associated with elevated hepatic lipase mass and activity. Here we report that Turks have low levels of high density lipoprotein subclass 2 (HDL(2)), apoA-I-containing lipoproteins (LpA-I), and pre-beta-1 HDL and increased levels of HDL(3) and LpA-I/A-II particles (potentially an atherogenic lipid profile). The frequency distributions of HDL-C and LpA-I levels were skewed toward bimodality in Turkish women but were unimodal in Turkish men.

Elevated hepatic lipase activity and low levels of high density lipoprotein in a normotriglyceridemic, nonobese Turkish population.

Low levels of high density lipoprotein cholesterol (HDL-C) are associated with increased risk of coronary heart disease and, in the United States, are often associated with hypertriglyceridemia and obesity. In Turkey, low HDL-C levels are highly prevalent, 53% of men and 26% of women having HDL-C levels <35 mg/dl, in the absence of hypertriglyceridemia and obesity. In this study to investigate the cause of low HDL-C levels in Turks, various factors affecting HDL metabolism were assessed in normotriglyceridemic Turkish men and women living in Istanbul and in non-Turkish men and women living in San Francisco.