Circulating microRNA in cardiovascular disease.

Acute myocardial infarction (AMI) and heart failure (HF) are two major causes of cardiovascular mortality and morbidity. Early diagnosis of these conditions is essential to instigate immediate treatment that may result in improved outcomes. Traditional biomarkers of AMI include cardiac troponins and other proteins released from the injured myocardium but there are a number of limitations with these biomarkers especially with regard to specificity.

Plasma insulin-like factor 3 (INSL3) in male patients with osteoporosis and Klinefelter's syndrome.

Insulin-like factor 3 (INSL3) is a peptide hormone produced in leydig cells of the testes. Its role in the adult male is unknown but INSL3 and its receptor RXFP2 have been linked to bone cell differentiation. It is speculated that low levels of INSL3 could be responsible for low bone mineral density in patients with primary osteoporosis and Klinefelter's Syndrome.

Changes in the concentrations of creatinine, cystatin C and NGAL in patients with acute paraquat self-poisoning.

An increase in creatinine > 3 μmol/L/h has been suggested to predict death in patients with paraquat self-poisoning and the value of other plasma biomarkers of acute kidney injury has not been assessed. The aim of this study was to validate the predictive value of serial creatinine concentrations and to study the utility of cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) as predictors of outcome in patients with acute paraquat poisoning. The rate of change of creatinine (dCr/dt) and cystatin C (dCyC/dt) concentrations were compared between survivors and deaths.

Genetic loci influencing kidney function and chronic kidney disease.

Using genome-wide association, we identify common variants at 2p12-p13, 6q26, 17q23 and 19q13 associated with serum creatinine, a marker of kidney function (P = 10(-10) to 10(-15)). Of these, rs10206899 (near NAT8, 2p12-p13) and rs4805834 (near SLC7A9, 19q13) were also associated with chronic kidney disease (P = 5.0 x 10(-5) and P = 3.

Pigmentation and vitamin D metabolism in Caucasians: low vitamin D serum levels in fair skin types in the UK.

Background: Vitamin D may play a protective role in many diseases. Public health messages are advocating sun avoidance to reduce skin cancer risk but the potential deleterious effects of these recommendations for vitamin D metabolism have been poorly investigated.

Methodology/principal Findings: We investigated the association between 25-hydroxy-vitamin D (25(OH)D), skin type and ultraviolet exposure in 1414 Caucasian females in the UK.

An obesogenic postnatal environment is more important than the fetal environment for the development of adult adiposity: a study of female twins.

Background: A relation between birth weight and adult body composition has been reported in singleton populations, especially when more accurate measures of body composition, such as dual-energy X-ray absorptiometry (DXA) were used. It remains uncertain whether this is mediated by a direct effect of fetal nutrition, through factors in the shared environment, or through genetic factors.

Objective: The objective was to investigate the relation between birth weight and body composition with the use of a co-twin design.

Epidemiology and genetic epidemiology of the liver function test proteins.

Background: The liver function test (LFT) is among the most commonly used clinical investigations to assess hepatic function, severity of liver diseases and the effect of therapies, as well as to detect drug-induced liver injury (DILI).

Aims: To determine the relative contribution of genetic and environmental factors as well as test and quantify the effects of sex, age, BMI and alcohol consumption to variation in liver function test proteins--including alanine amino transaminase (ALT), Albumin, gamma glutamyl transpeptidase (GGT), total bilirubin, total protein, total globulin, aspartate transaminase (AST), and alkaline phosphotase (ALP)--using the classical twin model.

Methods: Blood samples were collected from a total of 5380 twin pairs from the TwinsUK registry.

CD36 gene promoter polymorphisms are associated with low density lipoprotein-cholesterol in normal twins and after a low-calorie diet in obese subjects.

Common polymorphisms of the CD36 fatty acid transporter gene have been associated with lipid metabolism and cardiovascular disease. Association of a CD36 promoter single nucleotide polymorphism genotype with anthropometry and serum lipids was investigated in normal subjects, and in obese subjects during an 8-week low calorie diet and 6-month weight-maintenance period. 2728 normal female Twins UK subjects (mean body mass index 24.

Adiponectin gene ADIPOQ SNP associations with serum adiponectin in two female populations and effects of SNPs on promoter activity.

Adiponectin is an insulin sensitiser in muscle and liver, and low serum levels characterise obesity and insulin resistance. Eight tagging single nucleotide polymorphisms (tSNPs) in the ADIPOQ gene and promoter were selected, and association with serum adiponectin was tested, in two independent samples of Caucasian women: the Chingford Study (n = 808, mean age 62.8 +/- 5.

Association of common JAK2 variants with body fat, insulin sensitivity and lipid profile.

The leptin signal is transduced via the JAK2-STAT3 (Janus kinase 2-signal transducer and activator of transcription-3) pathway at the leptin receptor. JAK2 also phosphorylates insulin receptor substrate, integral to insulin and leptin action and is required for optimum adenosine triphosphate-binding cassette transporter A1 (ABCA1)-dependent transport of lipids from cells to apolipoprotein A-1 (apoA-I). We hypothesized that common variation in the JAK2 gene may be associated with body fat, insulin sensitivity, and modulation of the serum lipid profile in the general population.

Quantitative linkage analysis for pancreatic B-cell function and insulin resistance in a large twin cohort.

Objective: Insulin resistance and disturbed glucose homeostasis are key characteristics of metabolic syndrome, diabetes, and cardiovascular disease. The recent nonlinear computer version of homeostasis model assessment (HOMA)2 provides an appropriate and convenient assessment of glucose metabolism, enabling gene-mapping studies in large population samples.

Research Design And Methods: Fasting insulin and glucose concentration were measured in 758 dizygous and 305 monozygous nondiabetic female pairs from the St.

Relation of birth weight, body mass index, and change in size from birth to adulthood to insulin resistance in a female twin cohort.

Context And Objectives: Because an adverse intrauterine environment is thought to induce insulin resistance, our objective was to investigate the relationships between birth weight, BMI, and change in body size over the life course and insulin resistance. SETTING, DESIGN, AND PARTICIPANTS: We conducted a cross-sectional study in a cohort of 1194 female twins aged 18-74 yr. The relationship between birth weight and insulin resistance was analyzed using a regression method allowing for a simultaneous estimation of within- and between-pair influences.

Intra-individual variation in creatinine and cystatin C.

Background: Serum creatinine and cystatin C are measured in the assessment of glomerular filtration rate. Biological variation of an analyte is an important determinant of its usefulness. Intra-individual variation in serum creatinine and cystatin C in healthy subjects was determined in this study.

Intrauterine, environmental, and genetic influences in the relationship between birth weight and lipids in a female twin cohort.

Objective: To investigate the association between birth weight and lipid levels in a cohort of UK female twins.

Methods And Results: Birth weights and fasting blood lipid levels were available for 2900 women aged 18 to 80 years. Individual level regressions indicated that a 1-kg increase in birth weight was associated with a 0.

Identification of QTLs for serum lipid levels in a female sib-pair cohort: a novel application to improve the power of two-locus linkage analysis.

Using a novel approach for a two-locus model that provides a greatly increased power to detect multiple quantitative trait loci (QTLs) in simulated data, we identified in a sample of 961 female sib-pairs, three genome-wide significant QTLs for apolipoprotein A1 on chromosomes 8p21.1-q13.1 (LOD score 3.

Genetic and environmental influences on lipids, lipoproteins, and apolipoproteins: effects of menopause.

Objective: Levels of lipids and (apo)lipoproteins are known to increase after menopause, but it is unknown whether the genetic and environmental variability alters or whether lipids and (apo)lipoproteins are influenced by different genes before and after menopause.

Methods And Results: We studied 453 monozygotic and 1280 dizygotic pairs of female white twins recruited from the St. Thomas' UK Adult Twin Registry and measured total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), triglycerides, lipoprotein(a) [Lp(a)], apolipoprotein A1 (apoA1), and apolipoprotein B (apoB).

Defective nitric oxide production and functional renal reserve in patients with type 2 diabetes who have microalbuminuria of African and Asian compared with white origin.

Diabetic nephropathy is a leading cause of end-stage renal failure. Its incidence is higher and is increasing in persons of Indo-Asian and African-Caribbean (African-Asian) compared with those of white origin. Nitric oxide deficiency is associated with progressive renal disease.