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- Patin, Etienne, et al.
(författare)
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Natural variation in the parameters of innate immune cells is preferentially driven by genetic factors
- 2018
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Ingår i: Nature Immunology. - : Springer Science and Business Media LLC. - 1529-2908 .- 1529-2916. ; 19, s. 302-314
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Tidskriftsartikel (refereegranskat)abstract
- The quantification and characterization of circulating immune cells provide key indicators of human health and disease. To identify the relative effects of environmental and genetic factors on variation in the parameters of innate and adaptive immune cells in homeostatic conditions, we combined standardized flow cytometry of blood leukocytes and genome-wide DNA genotyping of 1,000 healthy, unrelated people of Western European ancestry. We found that smoking, together with age, sex and latent infection with cytomegalovirus, were the main non-genetic factors that affected variation in parameters of human immune cells. Genome-wide association studies of 166 immunophenotypes identified 15 loci that showed enrichment for disease-associated variants. Finally, we demonstrated that the parameters of innate cells were more strongly controlled by genetic variation than were those of adaptive cells, which were driven by mainly environmental exposure. Our data establish a resource that will generate new hypotheses in immunology and highlight the role of innate immunity in susceptibility to common autoimmune diseases.
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| 2. |
- Rogge, Barbara P., et al.
(författare)
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Effect of Overweight and Obesity on Cardiovascular Events in Asymptomatic Aortic Stenosis
- 2013
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 62:18, s. 1683-1690
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This study investigated whether overweight and obesity impacted outcome in patients with aortic valve stenosis (AS). Background Increased body mass index (BMI) is a strong predictor of higher cardiovascular (CV) morbidity and mortality in the general population but not among patients undergoing heart surgery. Methods Cardiovascular events in 1,664 patients with initially asymptomatic AS were recorded during a mean of 4.3 years of follow-up in the SEAS (Simvastatin Ezetimibe in Aortic Stenosis) study. Patients were grouped according to baseline BMI class. Results Overweight (n = 737) and obese patients (n = 334) had higher prevalence of hypertension, more abnormal left ventricular geometry, and lower stress-corrected midwall shortening throughout the study compared with normal weight patients (all p < 0.01). The AS progression rate did not differ between BMI classes. In univariate Cox regression, overweight was associated with a 17% to 22% lower rate of AS-related (p = 0.04) and ischemic CV events (p = 0.05). In multivariate analyses, adjusting for AS severity and differences in baseline characteristics, overweight had no significant influence on the rate of ischemic CV or AS-related events, whereas overweight and obesity had 46% and 67% higher rate of total mortality and 42% and 69% higher rate of combined hospital stay for heart failure and death from any cause, respectively, compared with normal weight patients (all p < 0.05). Conclusions In patients with initially asymptomatic AS participating in the SEAS study, overweight and obesity did not influence AS progression or rate of AS-related or ischemic CV events but were both associated with increased mortality. (C) 2013 by the American College of Cardiology Foundation
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