1,370 research outputs found

    The associations between bitter and fat taste sensitivity, and dietary fat intake: Are they impacted by genetic predisposition?

    Get PDF
    A relationship between bitter and fat taste sensitivity, CD36 rs1761667 and TAS2R38 has been demonstrated. However, research is scarce and does not take diet into account. This study aimed to explore associations between genetics, fat and bitter taste sensitivity and dietary fat intake in healthy UK adults. A cross-sectional study was carried out on 88 Caucasian participants (49 females and 39 males aged 35 ± 1 years; body mass index 24.9 ± 0.5 kg/m 2). Bitter taste sensitivity was assessed using phenylthiocarbamide (PTC) impregnated strips and the general Labelled Magnitude Scale. Fat taste sensitivity was assessed by the Ascending Forced Choice Triangle Procedure and dietary intake with a semi-quantitative food frequency questionnaire. Genotyping for rs713598, rs1726866, rs10246939 and rs1761667 was performed. Participants with TAS2R38 PAV/PAV diplotype perceived PTC strips as more bitter than groups carrying AVI haplotypes (AVI/AVI, p = 1x10 -6; AVI/AAV, p = 0.029). CD36 rs1761667 was associated with fat taste sensitivity (p = 0.008). A negative correlation between bitter taste sensitivity and saturated fat intake was observed (rs = -0.256, p = 0.016). When combining the CD36 genotypes and TAS2R38 diplotypes into one variable, participants carrying both TAS2R38 AVI haplotype and CD36 A allele had a higher intake of saturated fat compared to carriers of CD36 GG genotype or TAS2R38 PAV/PAV and PAV/AAV diplotypes (13.8 ± 0.3 vs 12.6 ± 0.5 %TEI, p = 0.047) warranting further exploration in a larger cohort

    The associations between bitter and fat taste sensitivity, and dietary fat intake: Are they impacted by genetic predisposition?

    Get PDF
    A relationship between bitter and fat taste sensitivity, CD36 rs1761667 and TAS2R38 has been demonstrated. However, research is scarce and does not take diet into account. This study aimed to explore associations between genetics, fat and bitter taste sensitivity and dietary fat intake in healthy UK adults. A cross-sectional study was carried out on 88 Caucasian participants (49 females and 39 males aged 35 ± 1 years; body mass index 24.9 ± 0.5 kg/m 2). Bitter taste sensitivity was assessed using phenylthiocarbamide (PTC) impregnated strips and the general Labelled Magnitude Scale. Fat taste sensitivity was assessed by the Ascending Forced Choice Triangle Procedure and dietary intake with a semi-quantitative food frequency questionnaire. Genotyping for rs713598, rs1726866, rs10246939 and rs1761667 was performed. Participants with TAS2R38 PAV/PAV diplotype perceived PTC strips as more bitter than groups carrying AVI haplotypes (AVI/AVI, p = 1x10 -6; AVI/AAV, p = 0.029). CD36 rs1761667 was associated with fat taste sensitivity (p = 0.008). A negative correlation between bitter taste sensitivity and saturated fat intake was observed (rs = -0.256, p = 0.016). When combining the CD36 genotypes and TAS2R38 diplotypes into one variable, participants carrying both TAS2R38 AVI haplotype and CD36 A allele had a higher intake of saturated fat compared to carriers of CD36 GG genotype or TAS2R38 PAV/PAV and PAV/AAV diplotypes (13.8 ± 0.3 vs 12.6 ± 0.5 %TEI, p = 0.047) warranting further exploration in a larger cohort

    BRCA2 polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers

    Get PDF
    Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10- 6) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for estrogen receptor–negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations

    Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis.

    Get PDF
    Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis

    Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

    Get PDF
    Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

    Get PDF
    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

    Get PDF
    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

    Get PDF
    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

    Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

    Get PDF
    Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

    AIDS-related mycoses: the way forward.

    Get PDF
    The contribution of fungal infections to the morbidity and mortality of HIV-infected individuals is largely unrecognized. A recent meeting highlighted several priorities that need to be urgently addressed, including improved epidemiological surveillance, increased availability of existing diagnostics and drugs, more training in the field of medical mycology, and better funding for research and provision of treatment, particularly in developing countries
    • …
    corecore