11 research outputs found
Causal effect of plasminogen activator inhibitor type 1 on coronary heart disease
Background: Plasminogen activator inhibitor type 1 (PAIā1) plays an essential role in the fibrinolysis system and thrombosis. Population studies have reported that blood PAIā1 levels are associated with increased risk of coronary heart disease (CHD). However, it is unclear whether the association reflects a causal influence of PAIā1 on CHD risk. Methods and Results: To evaluate the association between PAIā1 and CHD, we applied a 3āstep strategy. First, we investigated the observational association between PAIā1 and CHD incidence using a systematic review based on a literature search for PAIā1 and CHD studies. Second, we explored the causal association between PAIā1 and CHD using a Mendelian randomization approach using summary statistics from large genomeāwide association studies. Finally, we explored the causal effect of PAIā1 on cardiovascular risk factors including metabolic and subclinical atherosclerosis measures. In the systematic metaāanalysis, the highest quantile of blood PAIā1 level was associated with higher CHD risk comparing with the lowest quantile (odds ratio=2.17; 95% CI: 1.53, 3.07) in an ageā and sexāadjusted model. The effect size was reduced in studies using a multivariableāadjusted model (odds ratio=1.46; 95% CI: 1.13, 1.88). The Mendelian randomization analyses suggested a causal effect of increased PAIā1 level on CHD risk (odds ratio=1.22 per unit increase of logātransformed PAIā1; 95% CI: 1.01, 1.47). In addition, we also detected a causal effect of PAIā1 on elevating blood glucose and highādensity lipoprotein cholesterol. Conclusions: Our study indicates a causal effect of elevated PAIā1 level on CHD risk, which may be mediated by glucose dysfunction.C. Song ā¦ Deborah Lawler ā¦ Lyle J. Palmer ... et al. (CHARGE Consortium Hemostatic Factor Working Group; ICBP Consortium; CHARGE Consortium Subclinical Working Group
Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: a phase 3, randomised, open-label intergroup study
Patterns of Mortality in the Elderly in Chi Linh, Hai Duong, Vietnam, Period 2004ā2012
To consider an overview and prospect of therapy to hepatocellular injuries by using siRNA through history to the function of non-coading RNAs
Gene-centric meta-analyses of 108 912 individuals confirm known body mass index loci and reveal three novel signals
Recent genetic association studies have made progress in uncovering components of the genetic architecture of the body mass index (BMI). We used the ITMAT-Broad-Candidate Gene Association Resource (CARe) (IBC) array comprising up to 49 320 single nucleotide polymorphisms (SNPs) across ~2100 metabolic and cardiovascular-related loci to genotype up to 108 912 individuals of European ancestry (EA), African-Americans, Hispanics and East Asians, from 46 studies, to provide additional insight into SNPs underpinning BMI. We used a five-phase study design: Phase I focused on meta-analysis of EA studies providing individual level genotype data; Phase II performed a replication of cohorts providing summary level EA data; Phase III meta-analyzed results from the first two phases; associated SNPs from Phase III were used for replication in Phase IV; finally in Phase V, a multi-ethnic meta-analysis of all samples from four ethnicities was performed. At an array-wide significance (P < 2.40E-06), we identify novel BMI associations in loci translocase of outer mitochondrial membrane 40 homolog (yeast) - apolipoprotein E - apolipoprotein C-I (TOMM40-APOE-APOC1) (rs2075650, P = 2.95E-10), sterol regulatory element binding transcription factor 2 (SREBF2, rs5996074, P = 9.43E-07) and neurotrophic tyrosine kinase, receptor, type 2 [NTRK2, a brain-derived neurotrophic factor (BDNF) receptor gene, rs1211166, P = 1.04E-06] in the Phase IV meta-analysis. Of 10 loci with previous evidence for BMI association represented on the IBC array, eight were replicated, with the remaining two showing nominal significance. Conditional analyses revealed two independent BMI-associated signals in BDNF and melanocortin 4 receptor (MC4R) regions. Of the 11 array-wide significant SNPs, three are associated with gene expression levels in both primary B-cells and monocytes; with rs4788099 in SH2B adaptor protein 1 (SH2B1) notably being associated with the expression of multiple genes in cis. These multi-ethnic meta-analyses expand our knowledge of BMI genetics.Yiran Guo, Matthew B. Lanktree, Kira C. Taylor, Hakon Hakonarson, Leslie A. Lange ... Deborah Lawlor ... et al. (The IBC 50K SNP array BMI Consortium
Isocitrate dehydrogenase (IDH) mutant gliomas: A Society for Neuro-Oncology (SNO) consensus review on diagnosis, management, and future directions
Isocitrate dehydrogenase (IDH) mutant gliomas are the most common adult, malignant primary brain tumors diagnosed in patients younger than 50, constituting an important cause of morbidity and mortality. In recent years, there has been significant progress in understanding the molecular pathogenesis and biology of these tumors, sparking multiple efforts to improve their diagnosis and treatment. In this consensus review from the Society for Neuro-Oncology (SNO), the current diagnosis and management of IDH-mutant gliomas will be discussed. In addition, novel therapies, such as targeted molecular therapies and immunotherapies, will be reviewed. Current challenges and future directions for research will be discussed