81 research outputs found

    Insulin resistance genetic risk score and burden of coronary artery disease in patients referred for coronary angiography

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    AimsInsulin resistance associates with development of metabolic syndrome and risk of cardiovascular disease. The link between insulin resistance and cardiovascular disease is complex and multifactorial. Confirming the genetic link between insulin resistance, type 2 diabetes, and coronary artery disease, as well as the extent of coronary artery disease, is important and may provide better risk stratification for patients at risk. We investigated whether a genetic risk score of 53 single nucleotide polymorphisms known to be associated with insulin resistance phenotypes was associated with diabetes and burden of coronary artery disease.Methods and resultsWe genotyped patients with a coronary angiography performed in the capital region of Denmark from 2010-2014 and constructed a genetic risk score of the 53 single nucleotide polymorphisms. Logistic regression using quartiles of the genetic risk score was performed to determine associations with diabetes and coronary artery disease. Associations with the extent of coronary artery disease, defined as one-, two- or three-vessel coronary artery disease, was determined by multinomial logistic regression. We identified 4,963 patients, of which 17% had diabetes and 55% had significant coronary artery disease. Of the latter, 27%, 14% and 14% had one, two or three-vessel coronary artery disease, respectively. No significant increased risk of diabetes was identified comparing the highest genetic risk score quartile with the lowest. An increased risk of coronary artery disease was found for patients with the highest genetic risk score quartile in both unadjusted and adjusted analyses, OR 1.21 (95% CI: 1.03, 1.42, p = 0.02) and 1.25 (95% CI 1.06, 1.48, pConclusionsAmong patients referred for coronary angiography, only a strong genetic predisposition to insulin resistance was associated with risk of coronary artery disease and with a greater disease burden

    Association of genetic variants previously implicated in coronary artery disease with age at onset of coronary artery disease requiring revascularizations

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    BACKGROUND:The relation between burden of risk factors, familial coronary artery disease (CAD), and known genetic variants underlying CAD and low-density lipoprotein cholesterol (LDL-C) levels is not well-explored in clinical samples. We aimed to investigate the association of these measures with age at onset of CAD requiring revascularizations in a clinical sample of patients undergoing first-time coronary angiography. METHODS:1599 individuals (mean age 64 years [min-max 29-96 years], 28% women) were genotyped (from blood drawn as part of usual clinical care) in the Copenhagen area (2010-2014). The burden of common genetic variants was measured as aggregated genetic risk scores (GRS) of single nucleotide polymorphisms (SNPs) discovered in genome-wide association studies. RESULTS:Self-reported familial CAD (prevalent in 41% of the sample) was associated with -3.2 years (95% confidence interval -4.5, -2.2, p<0.0001) earlier need of revascularization in sex-adjusted models. Patients with and without familial CAD had similar mean values of CAD-GRS (unweighted scores 68.4 vs. 68.0, p = 0.10, weighted scores 67.7 vs. 67.5, p = 0.49) and LDL-C-GRS (unweighted scores 58.5 vs. 58.3, p = 0.34, weighted scores 63.3 vs. 61.1, p = 0.41). The correlation between the CAD-GRS and LDL-C-GRS was low (r = 0.14, p<0.001). In multivariable adjusted regression models, each 1 standard deviation higher values of LDL-C-GRS and CAD-GRS were associated with -0.70 years (95% confidence interval -1.25, -0.14, p = 0.014) and -0.51 years (-1.07, 0.04, p = 0.07) earlier need for revascularization, respectively. CONCLUSIONS:Young individuals presenting with CAD requiring surgical interventions had a higher genetic burden of SNPs relating to LDL-C and CAD (although the latter was statistically non-significant), compared with older individuals. However, the absolute difference was modest, suggesting that genetic screening can currently not be used as an effective prediction tool of when in life a person will develop CAD. Whether undiscovered genetic variants can still explain a "missing heritability" in early-onset CAD warrants more research

    The effect of exposure to synthetic pheromone lures on male Zygaena filipendulae mating behaviour: implications for monitoring species of conservation interest

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    Pheromone based monitoring of insects of conservation value has the potential to revolutionise the way in which surveys are carried out. However, due to their effective use in pest management, concerns have been raised about potential negative effects of pheromone exposure on populations of rare insects. The effect of exposure to synthetic pheromone lures on male mating behaviour was examined in laboratory and field conditions using the six spot burnet moth Zygaena filipendulae (Linnaeus, 1758). For the laboratory experiment larvae were collected and cultured separately under controlled conditions. Virgin males were exposed to a synthetic pheromone lure for 24 h; then tested for responsiveness immediately after this exposure, 1 and 24 h later. Control males were tested three times: initially, 1 h later and 24 h later. The time taken for males to detect females, shown by exposure of their anal claspers, and the time taken for males to locate females were recorded. No significant difference was found between the time taken for control and exposed males to detect or locate females, and no significant difference between the proportions of males that successfully located females in exposed and control groups was found. In the field experiment the time males spent in the presence of contained females, both with and without a pheromone lure present, was recorded. Males spent more time in the presence of the females when the pheromone lure was present. Both experiments indicate male Z. filipendulae mating behaviour is not adversely affected by exposure to synthetic pheromone lures

    Gene-Trap Mutagenesis Identifies Mammalian Genes Contributing to Intoxication by Clostridium perfringens ε-Toxin

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    The Clostridium perfringens ε-toxin is an extremely potent toxin associated with lethal toxemias in domesticated ruminants and may be toxic to humans. Intoxication results in fluid accumulation in various tissues, most notably in the brain and kidneys. Previous studies suggest that the toxin is a pore-forming toxin, leading to dysregulated ion homeostasis and ultimately cell death. However, mammalian host factors that likely contribute to ε-toxin-induced cytotoxicity are poorly understood. A library of insertional mutant Madin Darby canine kidney (MDCK) cells, which are highly susceptible to the lethal affects of ε-toxin, was used to select clones of cells resistant to ε-toxin-induced cytotoxicity. The genes mutated in 9 surviving resistant cell clones were identified. We focused additional experiments on one of the identified genes as a means of validating the experimental approach. Gene expression microarray analysis revealed that one of the identified genes, hepatitis A virus cellular receptor 1 (HAVCR1, KIM-1, TIM1), is more abundantly expressed in human kidney cell lines than it is expressed in human cells known to be resistant to ε-toxin. One human kidney cell line, ACHN, was found to be sensitive to the toxin and expresses a larger isoform of the HAVCR1 protein than the HAVCR1 protein expressed by other, toxin-resistant human kidney cell lines. RNA interference studies in MDCK and in ACHN cells confirmed that HAVCR1 contributes to ε-toxin-induced cytotoxicity. Additionally, ε-toxin was shown to bind to HAVCR1 in vitro. The results of this study indicate that HAVCR1 and the other genes identified through the use of gene-trap mutagenesis and RNA interference strategies represent important targets for investigation of the process by which ε-toxin induces cell death and new targets for potential therapeutic intervention

    Crossmodal correspondences between odors and contingent features: odors, musical notes, and geometrical shapes

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    Prediction of ground reaction forces and moments during sports-related movements

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    When performing inverse dynamic analysis (IDA) of musculoskeletal models to study human motion, inaccuracies in experimental input data and a mismatch between the model and subject lead to dynamic inconsistency. By predicting the ground reaction forces and moments (GRF&Ms) this inconsistency can be reduced and force plate measurements become unnecessary. In this study, a method for predicting GRF&Ms was validated for an array of sports-related movements. The method was applied to ten healthy subjects performing, for example, running, a side-cut manoeuvre, and vertical jump. Pearson’s correlation coefficient (r) and root-mean-square deviation were used to compare the predicted GRF&Ms and associated joint kinetics to the traditional IDA approach, where the GRF&Ms were measured using force plates. The main findings were that the method provided estimates comparable to traditional IDA across all movements for vertical GRFs (r ranging from 0.97 to 0.99, median 0.99), joint flexion moments (r ranging from 0.79 to 0.98, median 0.93), and resultant joint reaction forces (r ranging from 0.78 to 0.99, median 0.97). Considering these results, this method can be used instead of force plate measurements, hereby, facilitating IDA in sports science research and enabling complete IDA using motion analysis systems that do not incorporate force plate data

    Her odours make him deaf: crossmodal modulation of olfaction and hearing in a male moth

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    All animals have to cope with sensory conflicts arising from simultaneous input of incongruent data to different sensory modalities. Nocturnal activity in moths includes mate-finding behaviour by odour detection and bat predator avoidance by acoustic detection. We studied male moths that were simultaneously exposed to female sex pheromones indicating the presence of a potential mate, and artificial bat cries simulating a predation risk. We show that stimulation of one sensory modality can modulate the response to information from another, suggesting that behavioural thresholds are dynamic and depend on the behavioural context. The tendency to respond to bat sounds decreased as the quality and/or the amount of sex pheromone increased. The behavioural threshold for artificial bat cries increased by up to 40 dB when male moths where simultaneously exposed to female sex pheromones. As a consequence, a male moth that has detected the pheromone plume from a female will not try to evade an approaching bat until the bat gets close, hence incurring increased predation risk. Our results suggest that male moths' reaction to sensory conflicts is a trade-off depending on the relative intensity of the input to CNS from the two sensory modalities
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