TM6SF2 Determines Both the Degree of Lipidation and the Number of VLDL Particles Secreted by the Liver.

In 2014, exome-wide studies identified a glutamine176lysine (p.E167K) substitution in a protein of unknown function named transmembrane 6 superfamily member 2 (TM6SF2). The p.

Relationship of apolipoprotein(a) isoform size with clearance and production of lipoprotein(a) in a diverse cohort.

Lipoprotein(a) [Lp(a)] has two main proteins, apoB100 and apo(a). High levels of Lp(a) confer an increased risk for atherosclerotic cardiovascular disease. Most people have two circulating isoforms of apo(a) differing in their molecular mass, determined by the number of Kringle IV Type 2 repeats.

Micronutrient status of Palestinian school children following salt and flour fortification: a cross-sectional study.

Background: In 1996 and in 2006, Palestine initiated salt iodization and multiple micronutrient fortification of wheat flour, respectively as a strategy to prevent deficiencies of these nutrients. In 2009, we assessed the impact of these interventions on the health and nutritional status of schoolchildren residing in the West Bank.

Methods: We surveyed a sample of 22 schools run by the UN Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) and the Palestinian Government.

Double Burden of Undernutrition and Obesity in Palestinian Schoolchildren: A Cross-Sectional Study.

Background: The coexistence of underweight and overweight (double burden) remains a major problem in many developing countries. Little is known about the factors associated with the double burden of malnutrition in Palestinian children.

Objective: To assess factors associated with undernutrition and overnutrition in 1500 schoolchildren aged 5 to 16 years, in the West Bank.

Hypercholesterolemia and reduced HDL-C promote hematopoietic stem cell proliferation and monocytosis: studies in mice and FH children.

Previous studies have shown that mice with defects in cellular cholesterol efflux show hematopoietic stem cell (HSPC) and myeloid proliferation, contributing to atherogenesis. We hypothesized that the combination of hypercholesterolemia and defective cholesterol efflux would promote HSPC expansion and leukocytosis more prominently than either alone. We crossed Ldlr(-/-) with Apoa1(-/-) mice and found that compared to Ldlr(-/-) mice, Ldlr(-/-)/Apoa1(+/-) mice, with similar LDL-cholesterol levels but reduced HDL-cholesterol (HDL-C) levels, had expansion of HSPCs, monocytosis and neutrophilia.

Endothelial function in individuals with coronary artery disease with and without type 2 diabetes mellitus.

The goal of this study was to determine if individuals with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) had greater endothelial dysfunction (ED) than individuals with only CAD. Flow-mediated dilation (FMD), calculated as percentage increase in brachial artery diameter in response to postischemic blood flow, was measured after an overnight fast in 2 cohorts. The first cohort included 76 participants in the Northern Manhattan Study with CAD; 25 also had T2DM.

Measures of postprandial lipoproteins are not associated with coronary artery disease in patients with type 2 diabetes mellitus.

Individuals with type 2 diabetes mellitus (DM) characteristically have elevated fasting and postprandial (PP) plasma triglycerides (TG). Previous case-control studies indicated that PPTG levels predict the presence of coronary artery disease (CAD) in people without DM; however, the data for patients with DM are conflicting. Therefore, we conducted a case-control study in DM individuals, 84 with (+) and 80 without (-) CAD.

The apolipoprotein(a) gene: linkage disequilibria at three loci differs in African Americans and Caucasians.

Lipoprotein(a) (Lp(a)) is an independent, genetically regulated cardiovascular risk factor. Lp(a) plasma levels are largely determined by the apolipoprotein(a) (apo(a)) component, and differ across ethnicity. Although a number of polymorphisms in the apo(a) gene have been identified, apo(a) genetic regulation is not fully understood.

Change in lipid profile in celiac disease: beneficial effect of gluten-free diet.

Purpose: Celiac disease is associated with hypocholesterolemia, which is thought to contribute to a favorable cardiovascular risk profile. This led to suggestions that the diagnosis of celiac disease and its treatment with a gluten-free diet may result in elevation of the serum cholesterol level and worsen this risk profile. However, no study proves this in adults.

Protective effect of apolipoprotein E2 on coronary artery disease in African Americans is mediated through lipoprotein cholesterol.

We studied the relationship of apolipoprotein E (apoE) isoforms and coronary artery disease (CAD) in 224 African Americans and 326 Caucasians undergoing diagnostic coronary angiography. The presence of CAD was defined as >50% stenosis in at least one artery. ApoE allele frequencies were 0.

Effect of acute cocaine administration on the QTc interval of habitual users.

The proarrhythmic effects of cocaine may be mediated in part by its effects on cardiac repolarization properties. This study evaluated the acute effects of smoking cocaine 25 mg on the electrocardiograms of 14 habitual cocaine users during a 12-minute observation period. After cocaine administration, heart rate increased by a mean of 22 beats/min (p <0.

Apo[a] size and PNR explain African American-Caucasian differences in allele-specific apo[a] levels for small but not large apo[a].

Apolipoprotein [a] (apo[a]) gene size is a major predictor of lipoprotein [a] level. To determine genetic predictors of allele-specific apo[a] levels beyond gene size, we evaluated the upstream C/T and pentanucleotide repeat (PNR) polymorphisms. We determined apo[a] sizes, allele-specific apo[a] levels, and C/T and PNR in 215 Caucasians and 139 African Americans.

Treatment with high-dose simvastatin reduces secretion of apolipoprotein B-lipoproteins in patients with diabetic dyslipidemia.

HMG-CoA reductase inhibitors (statins) are effective lipid-altering drugs for the treatment of dyslipidemia in patients with type 2 diabetes mellitus. We conducted a randomized, double-blind, placebo-controlled, crossover design trial to determine the effects of simvastatin, 80 mg/day, on plasma lipid and lipoprotein levels and on the metabolism of apolipoprotein B (apoB) in VLDL, intermediate density lipoprotein (IDL), and LDL and of triglycerides (TGs) in VLDL. Simvastatin therapy decreased TG, cholesterol, and apoB significantly in VLDL, IDL, and LDL.

Postprandial response to a physiologic caloric load in HIV-positive patients receiving protease inhibitor-based or nonnucleoside reverse transcriptase inhibitor-based antiretroviral therapy.

Background: Features of the dyslipidemic pattern reported with the use of antiretroviral therapy predict enhanced postprandial lipemia, which is an emerging cardiovascular disease risk factor.

Objective: We evaluated the postprandial response to a physiologic, meal-based challenge in HIV-positive subjects without hyperlipidemia.

Design: We measured hourly lipid, lipoprotein, glucose, and insulin concentrations during a 13-h period in 25 nonwhite patients (13 women, 12 men): 13 receiving a protease inhibitor (PI)-based regimen (6 nelfinavir and 7 indinavir) and 12 receiving a nonnucleoside reverse transcriptase inhibitor (NNRTI)-based regimen (6 efavirenz and 6 nevirapine).

Cholesterol-lowering benefits of oat-containing cereal in Hispanic americans.

This randomized, controlled trial of cholesterol lowering by an oat bran cereal containing beta glucan vs a corn cereal without soluble fiber in Hispanic Americans was conducted for 11 weeks. One-hundred fifty-two men and women, ages 30 to 70 years, with baseline low-density lipoprotein cholesterol (LDL-C) levels between 120 and 190 mg/dL and triglycerides <400 mg/dL were included. After eating a National Cholesterol Education Program Step 1 diet for 5 weeks, subjects were randomly assigned to the corn or the oat cereal for the next 6 weeks.

Effects of the PPARgamma agonist pioglitazone on lipoprotein metabolism in patients with type 2 diabetes mellitus.

Elevated plasma levels of VLDL triglycerides (TGs) are characteristic of patients with type 2 diabetes mellitus (T2DM) and are associated with increased production rates (PRs) of VLDL TGs and apoB. Lipoprotein lipase-mediated (LPL-mediated) lipolysis of VLDL TGs may also be reduced in T2DM if the level of LPL is decreased and/or the level of plasma apoC-III, an inhibitor of LPL-mediated lipolysis, is increased. We studied the effects of pioglitazone (Pio), a PPARgamma agonist that improves insulin sensitivity, on lipoprotein metabolism in patients with T2DM.

Effect of gender on the manifestations of celiac disease: evidence for greater malabsorption in men.

Objective: Because celiac disease is a female-predominant disease we investigated the influence of gender on clinical manifestations of the disease in the United States.

Material And Methods: Data were obtained on biopsy-proven adult patients with celiac disease from a database of patients seen between 1981 and 2001 in a University-based referral center. Z scores were calculated to adjust for age, ethnicity and gender using the National Health and Nutrition Examination Survey database as controls.

Autonomic modulation of the u wave during sympathomimetic stimulation and vagal inhibition in normal individuals.

Prolonged repolarization time, an important contributor to the pathogenesis of ventricular arrhythmias, is usually identified by a long QT interval (QT) on the ECG but is frequently confounded by the presence of a U wave. The physiological basis and clinical relevance of the U wave is unresolved. To better understand the relationship between the T and U waves, this study examined their behavior during nonresting autonomic conditions.

Sample size determination.

Scientists who use animals in research must justify the number of animals to be used, and committees that review proposals to use animals in research must review this justification to ensure the appropriateness of the number of animals to be used. This article discusses when the number of animals to be used can best be estimated from previous experience and when a simple power and sample size calculation should be performed. Even complicated experimental designs requiring sophisticated statistical models for analysis can usually be simplified to a single key or critical question so that simple formulae can be used to estimate the required sample size.

Autonomic nervous system influences on QT interval in normal subjects.

Objectives: We sought to determine whether the relationship between heart rate (HR) and QT interval (QT) differs as HR increases in response to exercise, atropine and isoproterenol.

Background: Autonomic nervous system influences on repolarization are poorly understood and may complicate the interpretation of QT measurements.

Methods: Twenty-five normal subjects sequentially underwent graded-intensity bicycle exercise, atropine injection and isoproterenol infusion.

Apolipoprotein [a] genotype influences isoform dominance pattern differently in African Americans and Caucasians.

Plasma lipoprotein [a] (Lp[a]) concentrations are inversely associated with, and largely determined by, apolipoprotein [a] (apo[a]) gene size, a highly polymorphic trait. We studied if, within an individual, the smaller apo[a] isoform always dominated, whether there was interaction between the two alleles, and whether these features differed between Caucasians and African Americans. We determined apo[a] gene sizes, apo[a] protein sizes and relative amounts, and plasma Lp[a] levels in 430 individuals (263 Caucasians and 167 African Americans).