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Träfflista för sökning "WFRF:(Gent J.) "

Sökning: WFRF:(Gent J.)

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  • Schofield, James P. R., et al. (författare)
  • Stratification of asthma phenotypes by airway proteomic signatures
  • 2019
  • Ingår i: Journal of Allergy and Clinical Immunology. - Elsevier. - 0091-6749 .- 1097-6825. ; 144:1, s. 70-82
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Stratification by eosinophil and neutrophil counts increases our understanding of asthma and helps target therapy, but there is room for improvement in our accuracy in prediction of treatment responses and a need for better understanding of the underlying mechanisms. Objective: We sought to identify molecular subphenotypes of asthma defined by proteomic signatures for improved stratification. Methods: Unbiased label-free quantitative mass spectrometry and topological data analysis were used to analyze the proteomes of sputum supernatants from 246 participants (206 asthmatic patients) as a novel means of asthma stratification. Microarray analysis of sputum cells provided transcriptomics data additionally to inform on underlying mechanisms. Results: Analysis of the sputum proteome resulted in 10 clusters (ie, proteotypes) based on similarity in proteomic features, representing discrete molecular subphenotypes of asthma. Overlaying granulocyte counts onto the 10 clusters as metadata further defined 3 of these as highly eosinophilic, 3 as highly neutrophilic, and 2 as highly atopic with relatively low granulocytic inflammation. For each of these 3 phenotypes, logistic regression analysis identified candidate protein biomarkers, and matched transcriptomic data pointed to differentially activated underlying mechanisms. Conclusion: This study provides further stratification of asthma currently classified based on quantification of granulocytic inflammation and provided additional insight into their underlying mechanisms, which could become targets for novel therapies.
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  • Stolk, Lisette, et al. (författare)
  • Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways
  • 2012
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 44:3, s. 260-268
  • Tidskriftsartikel (refereegranskat)abstract
    • To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 × 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-κB signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
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  • Gast, Gerrie-Cor M, et al. (författare)
  • Hormone therapy and coronary heart disease risk by vasomotor menopausal symptoms.
  • 2011
  • Ingår i: Maturitas. - Elsevier. - 1873-4111. ; 70:4, s. 373-378
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: We examined whether the association between hormone therapy (HT) use and coronary heart disease (CHD) risk differed between women with and without vasomotor symptoms (VMS). STUDY DESIGN: We used data from a Dutch (EPOS) and Swedish (WHILA) population-based sample of 8865 women, aged 46-64 years, and free of CHD, stroke, venous thrombosis/pulmonary embolism or cancer at baseline. Data on HT use, VMS and potential confounders were collected by questionnaires. MAIN OUTCOME MEASURES: CHD endpoints, obtained via registries. RESULTS: 252 CHD cases occurred during 10.3 years of follow-up. Neither for women with nor for women without flushing or (night) sweats ever HT use was associated with CHD risk, compared with never HT use. Among women with intense VMS, ever HT use borderline significantly decreased CHD risk compared with never HT use (HR 0.48 [95% CI 0.20-1.03]). Among women without intense VMS, ever HT use was associated with a borderline significant increased CHD risk (HR 1.28 [95% CI 0.96-1.70]; P for interaction=0.02). However, after multivariate adjustment, as compared to never HT use, ever HT use was not associated with risk of CHD among women with or without intense VMS. CONCLUSIONS: In both groups of women with and without VMS, HT use does not seem to be associated with the risk of CHD. Hence, our findings do not support the view that HT use increases the CHD risk among women with an indication, i.e. VMS, but this needs to be confirmed in specifically designed studies.
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  • Gast, Gerrie-Cor M, et al. (författare)
  • Menopausal Complaints Are Associated With Cardiovascular Risk Factors.
  • 2008
  • Ingår i: Hypertension. - Lippincott Williams & Wilkins. - 1524-4563. ; 51:6, s. 1492-1498
  • Tidskriftsartikel (refereegranskat)abstract
    • It has been hypothesized that women with vasomotor symptoms differ from those without with respect to cardiovascular risk factors or responses to exogenous hormone therapy. We studied whether the presence and extent of menopausal complaints are associated with cardiovascular risk profile. Data were used from a population-based sample of 5523 women, aged 46 to 57 years, enrolled between 1994 and 1995. Data on menopausal complaints and potential confounders were collected by questionnaires. Total cholesterol, systolic and diastolic blood pressures, and body mass index were measured. Linear and logistic regression analyses were used to analyze the data. Night sweats were reported by 38% and flushing by 39% of women. After multivariate adjustment, women with complaints of flushing had a 0.27-mmol/L (95% CI: 0.15 to 0.39) higher cholesterol level, a 0.60-kg/m(2) (95% CI: 0.35 to 0.84) higher BMI, a 1.59-mm Hg (95% CI: 0.52 to 2.67) higher systolic blood pressure, and a 1.09-mm Hg (95% CI: 0.48 to 1.69) higher diastolic blood pressure compared with asymptomatic women. Flushing was also associated with hypercholesterolemia (odds ratio: 1.52; 95% CI: 1.25 to 1.84) and hypertension (OR: 1.20; 95% CI: 1.07 to 1.34). Results were similar for complaints of night sweating. The findings support the view that menopausal complaints are associated with a less favorable cardiovascular risk profile. These findings substantiate the view that differences in the presence of menopausal symptoms as a reason for using hormone therapy could explain discrepant findings between observational research and trials.
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  • Gast, Gerrie-Cor M, et al. (författare)
  • Vasomotor menopausal symptoms are associated with increased risk of coronary heart disease.
  • 2011
  • Ingår i: Menopause. - Lippincott-Raven Publishers. - 1530-0374. ; 18, s. 146-151
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE:: Emerging evidence suggests that women with vasomotor menopausal symptoms (VMS) may have an adverse cardiovascular disease (CVD) risk profile. We investigated whether VMS are related to an increased risk of future coronary heart disease (CHD) and whether possible associations can be explained by CVD risk factors. METHODS:: Data used were from a Dutch and Swedish population-based sample of 10,787 women enrolled between 1995 and 2000, aged 46 to 64 years, and free of CVD at baseline. Data on VMS were collected by questionnaires. Body mass index and blood pressure were measured in all women, and total cholesterol levels were measured in a subgroup of the population. Multivariable Cox regression models were used to analyze the data. RESULTS:: After a mean ± SD follow-up period of 10.3 ± 2.1 years, 303 women were diagnosed with CHD. Symptoms of flushing were not associated with risk of CHD. However, the presence of night sweats was associated with a significantly modest increased risk of CHD, with a multivariable-adjusted hazard ratio of 1.33 (95% CI, 1.05-1.69). This association was attenuated but not eliminated after correction for body mass index, blood pressure, and total cholesterol (hazard ratio, 1.25; 95% CI, 0.99-1.58). CONCLUSIONS:: Women with menopausal symptoms of night sweats have a significantly moderately increased risk of CHD, which cannot be totally explained by the levels of CVD risk factors.
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