Genetic variation in thioredoxin interacting protein (TXNIP) is associated with hypertriglyceridaemia and blood pressure in diabetes mellitus.

Aims: Thioredoxin interacting protein (TXNIP) is an attractive candidate gene for diabetes or diabetic dyslipidaemia, since TXNIP is the strongest glucose-responsive gene in pancreatic B-cells, TXNIP deficiency in a mouse model is associated with hyperlipidaemia and TXNIP is located in the 1q21-1q23 chromosomal Type 2 diabetes mellitus (DM) locus. We set out to investigate whether metabolic effects of TXNIP that were previously reported in a murine model are also relevant in human Type 2 DM.

Methods: The frequency distribution of a 3' UTR single nucleotide polymorphism (SNP) in TXNIP was investigated in subjects with normal glucose tolerance (NGT; n = 379), impaired glucose tolerance (IGT; n = 228) and Type 2 DM (n = 230).

Heritability and genetic loci of fatty liver in familial combined hyperlipidemia.

VLDL overproduction, a process that is driven by an excess amount of hepatic fat, is a well-documented feature of familial combined hyperlipidemia (FCHL). The aims of this study were to investigate whether fatty liver, measured with ultrasound and as plasma alanine aminotransferase (ALT) levels, develops against a genetic background in FCHL and to identify chromosomal loci that are linked to these traits. In total, 157 FCHL family members and 20 spouses participated in this study.

Fatty liver is an integral feature of familial combined hyperlipidaemia: relationship with fat distribution and plasma lipids.

Overproduction of VLDL (very-low-density lipoprotein) particles is an important cause of FCHL (familial combined hyperlipidaemia). It has been shown recently that VLDL production is driven by the amount of hepatic fat. The present study was conducted to determine the prevalence of fatty liver in relation to the different fat compartments and lipid parameters in FCHL.

Direct association of a promoter polymorphism in the CD36/FAT fatty acid transporter gene with Type 2 diabetes mellitus and insulin resistance.

Aims: The membrane-bound fatty acid transporter CD36/FAT may play a role in disturbed fatty acid handling as observed in the metabolic syndrome and Type 2 diabetes mellitus (T2DM). Genetic variation in the CD36 gene may contribute to the aetiology of diabetes.

Methods: A population-based cohort in the Netherlands [age > 40 years and body mass index (BMI) > 25 kg/m2] of 675 subjects was phenotyped with respect to glucose metabolism with an oral glucose tolerance test and was genotyped for a known 478C-->T substitution and a C/T snp in the upstream promoter region (rs1527479) in the CD36 gene.

Up-regulation of CD36/FAT in preadipocytes in familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) shows many features of the metabolic syndrome. The strong genetic component makes it an excellent model to study the genetic background of metabolic syndrome and insulin resistance. Adipose tissue is believed to contribute to, or even underlie, the FCHL phenotype and is an interesting target tissue for gene expression studies.

Abdominal obesity and expression of familial combined hyperlipidemia.

Objective: To investigate the role of abdominal and body obesity on the prevalence of hyperlipidemia, in particular, hypertriglyceridemia, hypercholesterolemia, and high apolipoprotein B levels, in familial combined hyperlipidemia (FCHL) relatives and their spouses.

Research Methods And Procedures: In FCHL relatives (n = 618) and spouses (n = 297), prevalence data of hyperlipidemia and high apolipoprotein B levels and their age and gender-corrected odds ratios (ORs) were calculated for sex-adjusted categories of waist-to-hip ratio (WHR), waist circumference, and BMI.

Results: Increments of BMI, waist circumference, and WHR increased the frequency of hyperlipidemia.

Steroid hormone synthesis in pregnancy.

The goal of this article is to summarize what is known about the pathways of steroid hormone synthesis and metabolism in human pregnancy. Emphasis is placed on the distinctions between steroidogenic pathways in adults and those that are operative during human pregnancy.

Differential gene expression of blood-derived cell lines in familial combined hyperlipidemia.

Objectives: The genetic background of familial combined hyperlipidemia (FCHL) is currently unclear. We propose transcriptional profiling as a complementary tool for its understanding. Two hypotheses were tested: the existence of a disease-specific modification of gene expression in FCHL and the detectability of such a transcriptional profile in blood derived cell lines.

Prothrombotic markers in familial combined hyperlipidemia: evidence of endothelial cell activation and relation to metabolic syndrome.

Background: Familial combined hyperlipidemia (FCHL) is characterized by a varied expression of hypertriglyceridemia and hypercholesterolemia within a family, and a high risk of premature coronary artery disease. The present study evaluated a number of potential prothrombotic markers in familial combined hyperlipidemia, and studied their relationship to the hypercholesterolemic (Fredrickson type IIa) and hypertriglyceridemic (IIb and IV) phenotypes.

Methods And Results: Selected prothrombotic markers were studied in 68 subjects: 34 hyperlipidemic subjects with familial combined hyperlipidemia and 34 controls.

Subclasses of low-density lipoprotein and very low-density lipoprotein in familial combined hyperlipidemia: relationship to multiple lipoprotein phenotype.

Objective: The present study addresses the presence of distinct metabolic phenotypes in familial combined hyperlipidemia (FCHL) in relation to small dense low-density lipoprotein (sd LDL) and very low-density lipoprotein (VLDL) subclasses.

Methods And Results: Hyperlipidemic FCHL relatives (n=72) were analyzed for LDL size by gradient gel electrophoresis. Pattern B LDL (sd LDL, particle size <258 A) and pattern A LDL (buoyant LDL, particle size > or =258 A) were defined.

Variants in the PPARgamma gene affect fatty acid and glycerol metabolism in familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is a common genetic lipid disorder characterized by premature coronary artery disease, dyslipidemia, insulin resistance, and impaired adipose tissue free fatty acid (FFA) metabolism. Increased adipose tissue FFA flux towards the liver may, in part, contribute to reduced insulin sensitivity and hyperlipidemia in FCHL. It was the objective of the present study to evaluate the contribution of the peroxisome proliferator-activated receptor gamma (PPARgamma) gene to FCHL traits related to adipocyte lipid metabolism, dyslipidemia, and insulin resistance.

[Atopic keratoconjunctivitis: probably a risk factor for the development of conjuntival carcinoma].

Background: Almost half of the patients with atopic dermatitis experience chronic inflammation of the eyelids, the conjunctiva and the cornea. Chronic inflammation is a possible cause for the development of malignancies, especially if associated with some kind of immunological defect as in atopic patients. So far, a correlation between atopic conjunctivitis and conjunctival malignancies has not yet been reported.

Immune testing in fertility practice: truth or deception?

Purpose Of Review: Much attention has been paid to the role of immunology in reproductive success or failure. Every step in the establishment of normal pregnancy has been implicated as a possible site of immune-mediated reproductive failure. The widespread testing of antiphospholipid, antinuclear, antithyroid, and antisperm antibodies, as well as generalized immune testing, have thus been employed to diagnose patients with otherwise unexplained infertility or recurrent pregnancy loss.

Identification of the PPARA locus on chromosome 22q13.3 as a modifier gene in familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is a common genetic lipid disorder that is present in 10% of patients with premature coronary artery disease (CAD). It was the objective of the present study to evaluate the possible involvement of the PPARA locus in the pathophysiology of FCHL. Mutation detection analyses of the six coding PPARA exons resulted in the identification of four novel variants, [C/T] intron 3, S234G, [G/A] intron 5, and [C/A] 3(') UTR in three FCHL probands, whereas no novel variants were identified in spouses.

Identification of differentially expressed genes in subcutaneous adipose tissue from subjects with familial combined hyperlipidemia.

Subjects with familial combined hyperlipidemia (FCHL) are characterized by a complex metabolic phenotype with hyperlipidemia, insulin resistance, and central obesity. FCHL is due to impaired adipose tissue function superimposed on hepatic overproduction of lipoproteins. We investigated adipose tissue as an interesting target tissue for differential gene expression in FCHL.

Locus for elevated apolipoprotein B levels on chromosome 1p31 in families with familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCH), a common cause of premature coronary artery disease, is genetically complex and poorly understood. Recently, a major locus on chromosome 1q21-23 exhibiting highly significant linkage was identified in Finnish FCH families by use of a parametric analysis. We now report highly significant evidence of linkage (maximum LOD score 3.

Topical mitomycin C and radiation induce conjunctival DNA-polyploidy.

Introduction: Atypical cell changes often occur following treatment of premalignant or malignant conjunctival neoplasias with topical mitomycin C (MMC) and/or radiation. These reactive, non-neoplastic alterations of the conjunctival epithelium can be a differential diagnostic problem. Our aim was to investigate changes in the nuclear DNA-distribution of conjunctival epithelial cells after MMC- and radiation therapy by DNA-image-cytometry.

Genetic dissection of familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is the most common genetic hyperlipidemia in man. FCHL is characterized by familial clustering of hyperlipidemia and clinical manifestations of premature coronary heart disease, i.e.

Soluble receptors for tumor necrosis factor-alpha (TNF-R p55 and TNF-R p75) in familial combined hyperlipidemia.

We investigated the potential role of the 75 kD receptor for tumor necrosis factor-alpha (TNF-alpha) (TNFRSF1B, located on chromosome 1 band p36.2) as a modifier gene in familial combined hyperlipidemia (FCH), based on previous linkage and association data. Age-corrected values for the soluble (s) extracellular domain of TNF-R p75 were lower in 156 well-characterized hyperlipidemic (HL) FCH relatives than in 168 normolipidemic (NL) relatives (P<0.

Identification of TNFRSF1B as a novel modifier gene in familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is the most commonly inherited hyperlipidemia in man, with a frequency of +/-1% in the general population and approximately 10% in myocardial infarction survivors. A genomic scan in 18 Dutch FCHL families resulted in the identification of several loci with evidence for linkage. One of these regions, 1p36.

Aetiology of heart failure as seen from a National Cardiac Referral Centre in Africa.

572 consecutive patients with heart failure referred to the National Cardiothoracic Centre, Accra, Ghana, over a 4-year period were evaluated for the aetiology of heart failure using two-dimensional Doppler echocardiography with colour flow. The mean age of the subjects with heart failure was 42.3 +/- 0.