The flame retardant DE-71 (a mixture of polybrominated diphenyl ethers) inhibits human differentiated thyroid cell function <i>in vitro</i>

Normal thyroid function is essential for general growth and metabolism, but can be affected by endocrine disrupting chemicals (EDCs). Polybrominated diphenyl ethers (PBDEs) have been used worldwide to reduce flammability in different materials and are suspected to be EDCs. The production of the commercial Penta- and OctaBDE mixtures is banned, but DecaBDEs and existing products may leak PBDEs into the environment. Our aim was to investigate the effect of the PentaBDE mixture DE-71 on human thyroid cells in vitro.Primary human thyroid cells were obtained as paraadenomatous tissue and cultured in monolayers. The influence of DE-71 on cyclic adenosine monophosphate (cAMP) and thyroglobulin (Tg) production was examined in the culture medium by competitive radioimmunoassay and enzyme-linked immunosorbent assay, respectively. Real-time quantitative PCR analysis of thyroid-specific genes was performed on the exposed cell cultures. PBDE concentrations were determined in cellular and supernatant fractions of the cultures.DE-71 inhibited Tg-release from TSH-stimulated thyrocytes. At 50 mg/L DE-71, mean Tg production was reduced by 71.9% (range: 8.5-98.7%), and cAMP by 95.1% (range: 91.5-98.8%) compared to controls). Expression of mRNA encoding Tg, TPO and TSHr were significantly inhibited (p<0.0001, p = 0.0079, and p = 0.0002, respectively). The majority of DE-71 added was found in the cell fraction. No cytotoxicity was found.DE-71 inhibited differentiated thyroid cell functions in a two phase response manner and a concentration-dependent inhibition of Tg and cAMP production, respectively, as well as expression of mRNA encoding Tg, TPO and TSHr. Our findings suggest an inhibiting effect of PBDEs on thyroid cells

Thyroid dysfunction and electrocardiographic changes in subjects without arrhythmias:a cross-sectional study of primary healthcare subjects from Copenhagen

ObjectiveThe objective of the present study was to investigate associations of both overt and subclinical thyroid dysfunction with common ECG parameters in a large primary healthcare population.DesignCross-sectional study.Setting and participantsThe study population comprised of primary healthcare patients in Copenhagen, Denmark, who had a thyroid function test and an ECG recorded within 7 days of each other between 2001 and 2011.Data sourcesThe Danish National Patient Registry was used to collect information regarding baseline characteristics and important comorbidities.Outcome measure and study groupsCommon ECG parameters were determined using Marquette 12SL software and were compared between the study groups. The study population was divided into five groups based on their thyroid status. Euthyroid subjects served as the reference group in all analyses.ResultsA total of 132 707 patients (age 52±17 years; 50% female) were included. Hyperthyroidism was significantly associated with higher heart rate and prolonged QTc interval with significant interaction with age (p&lt;0.009) and sex (p&lt;0.001). These associations were less pronounced for patients with higher age. Subclinical hyperthyroidism was associated with higher heart rate among females, and a similar trend was observed among males. Hypothyroidism was associated with slower heart rate and shorter QTc but only in women. Moreover, longer P-wave duration, longer PR interval and low voltage were observed in patients with both subclinical and overt hypothyroidism. However, the presence of low voltage was less pronounced with higher age (p=0.001).ConclusionBoth overt and subclinical thyroid disorders were associated with significant changes in important ECG parameters. Age and gender have significant impact on the association of thyroid dysfunction particularly on heart rate and QTc interval

Association between FTO variant and change in body weight and its interaction with dietary factors: the DiOGenes study

Although FTO is an established obesity-susceptibility locus, it remains unknown whether it influences weight change in adult life and whether diet attenuates this association. Therefore, we investigated the association of FTO-rs9939609 with changes in weight and waist circumference (WC) during 6.8 years follow-up in a large-scale prospective study and examined whether these associations were modified by dietary energy percentage from fat, protein, carbohydrate, or glycemic index (GI). This study comprised data from five countries of European Prospective Investigation into Cancer and Nutrition (EPIC) and was designed as a case-cohort study for weight gain. Analyses included 11,091 individuals, of whom 5,584 were cases (age (SD), 47.6 (7.5) years), defined as those with the greatest unexplained annual weight gain during follow-up and 5,507 were noncases (48.0 (7.3) years), who were compared in our case-noncase (CNC) analyses. Furthermore, 6,566 individuals (47.9 (7.3) years) selected from the total sample (all noncases and 1,059 cases) formed the random subcohort (RSC), used for continuous trait analyses. Interactions were tested by including interaction terms in the models. In the RSC-analyses, FTO-rs9939609 was associated with BMI (β (SE), 0.17 (0.08) kg·m(-2)/allele; P = 0.034) and WC (0.47 (0.21) cm/allele; P = 0.026) at baseline, but not with weight change (5.55 (12.5) g·year(-1)/allele; P = 0.66) during follow up. In the CNC-analysis, FTO-rs9939609 was associated with increased risk of being a weight-gainer (OR: 1.1; P = 0.045). We observed no interaction between FTO-rs9939609 and dietary fat, protein and carbohydrate, and GI on BMI and WC at baseline or on change in weight and WC. FTO-rs9939609 is associated with BMI and WC at baseline, but association with weight gain is weak and only observed for extreme gain. Dietary factors did not influence the associations

The Center for Integrated Molecular Brain Imaging (Cimbi) database

AbstractWe here describe a multimodality neuroimaging containing data from healthy volunteers and patients, acquired within the Lundbeck Foundation Center for Integrated Molecular Brain Imaging (Cimbi) in Copenhagen, Denmark. The data is of particular relevance for neurobiological research questions related to the serotonergic transmitter system with its normative data on the serotonergic subtype receptors 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT4 and the 5-HT transporter (5-HTT), but can easily serve other purposes.The Cimbi database and Cimbi biobank were formally established in 2008 with the purpose to store the wealth of Cimbi-acquired data in a highly structured and standardized manner in accordance with the regulations issued by the Danish Data Protection Agency as well as to provide a quality-controlled resource for future hypothesis-generating and hypothesis-driven studies.The Cimbi database currently comprises a total of 1100 PET and 1000 structural and functional MRI scans and it holds a multitude of additional data, such as genetic and biochemical data, and scores from 17 self-reported questionnaires and from 11 neuropsychological paper/computer tests. The database associated Cimbi biobank currently contains blood and in some instances saliva samples from about 500 healthy volunteers and 300 patients with e.g., major depression, dementia, substance abuse, obesity, and impulsive aggression. Data continue to be added to the Cimbi database and biobank

FTO Gene Associated Fatness in Relation to Body Fat Distribution and Metabolic Traits throughout a Broad Range of Fatness

A common single nucleotide polymorphism (SNP) of FTO (rs9939609, T/A) is associated with total body fatness. We investigated the association of this SNP with abdominal and peripheral fatness and obesity-related metabolic traits in middle-aged men through a broad range of fatness present already in adolescence.Obese young Danish men (n = 753, BMI > or = 31.0 kg/m(2)) and a randomly selected group (n = 879) from the same population were examined in three surveys (mean age 35, 46 and 49 years, respectively). The traits included anthropometrics, body composition, oral glucose tolerance test, blood lipids, blood pressure, fibrinogen and aspartate aminotransferase. Logistic regression analysis was used to assess the age-adjusted association between the phenotypes and the odds ratios for the FTO rs9939609 (TT and TA genotype versus the AA genotype), for anthropometrics and body composition estimated per unit z-score. BMI was strongly associated with the AA genotype in all three surveys: OR = 1.17, p = 1.1*10(-6), OR = 1.20, p = 1.7*10(-7), OR = 1.17, p = 3.4*10(-3), respectively. Fat body mass index was also associated with the AA genotype (OR = 1.21, p = 4.6*10(-7) and OR = 1.21, p = 1.0*10(-3)). Increased abdominal fatness was associated with the AA genotype when measured as waist circumference (OR = 1.21, p = 2.2*10(-6) and OR = 1.19, p = 5.9*10(-3)), sagittal abdominal diameter (OR = 1.17, p = 1.3*10(-4) and OR = 1.18, p = 0.011) and intra-abdominal adipose tissue (OR = 1.21, p = 0.005). Increased peripheral fatness measured as hip circumference (OR = 1.19, p = 1.3*10(-5) and OR = 1.18, p = 0.004) and lower body fat mass (OR = 1.26, p = 0.002) was associated with the AA genotype. The AA genotype was significantly associated with decreased Stumvoll insulin sensitivity index (OR = 0.93, p = 0.02) and with decreased non-fasting plasma HDL-cholesterol (OR = 0.57, p = 0.037), but not with any other of the metabolic traits. However, all significant results for both body fat distribution and metabolic traits were explained by a mediating effect of total fat mass.The association of the examined FTO SNP to general fatness throughout the range of fatness was confirmed, and this association explains the relation between the SNP and body fat distribution and decreased insulin sensitivity and HDL-cholesterol. The SNP was not significantly associated with other metabolic traits suggesting that they are not derived from the general accumulation of body fat

Fatness-Associated FTO Gene Variant Increases Mortality Independent of Fatness – in Cohorts of Danish Men

The A-allele of the single nucleotide polymorphism (SNP), rs9939609, in the FTO gene is associated with increased fatness. We hypothesized that the SNP is associated with morbidity and mortality through the effect on fatness.In a population of 362,200 Danish young men, examined for military service between 1943 and 1977, all obese (BMI>or=31.0 kg/m(2)) and a random 1% sample of the others were identified. In 1992-94, at an average age of 46 years, 752 of the obese and 876 of the others were re-examined, including measurements of weight, fat mass, height, and waist circumference, and DNA sampling. Hospitalization and death occurring during the following median 13.5 years were ascertained by linkage to national registers. Cox regression analyses were performed using a dominant effect model (TT vs. TA or AA). In total 205 men died. Mortality was 42% lower (p = 0.001) with the TT genotype than in A-allele carriers. This phenomenon was observed in both the obese and the randomly sampled cohort when analysed separately. Adjustment for fatness covariates attenuated the association only slightly. Exploratory analyses of cause-specific mortality and morbidity prior to death suggested a general protective effect of the TT genotype, whereas there were only weak associations with disease incidence, except for diseases of the nervous system.Independent of fatness, the A-allele of the FTO SNP appears to increase mortality of a magnitude similar to smoking, but without a particular underlying disease pattern barring an increase in the risk of diseases of the nervous system