The Variant rs1867277 in FOXE1 Gene Confers Thyroid Cancer Susceptibility through the Recruitment of USF1/USF2 Transcription Factors

In order to identify genetic factors related to thyroid cancer susceptibility, we adopted a candidate gene approach. We studied tag- and putative functional SNPs in genes involved in thyroid cell differentiation and proliferation, and in genes found to be differentially expressed in thyroid carcinoma. A total of 768 SNPs in 97 genes were genotyped in a Spanish series of 615 cases and 525 controls, the former comprising the largest collection of patients with this pathology from a single population studied to date. SNPs in an LD block spanning the entire FOXE1 gene showed the strongest evidence of association with papillary thyroid carcinoma susceptibility. This association was validated in a second stage of the study that included an independent Italian series of 482 patients and 532 controls. The strongest association results were observed for rs1867277 (OR[per-allele] = 1.49; 95%CI = 1.30–1.70; P = 5.9×10−9). Functional assays of rs1867277 (NM_004473.3:c.−283G>A) within the FOXE1 5′ UTR suggested that this variant affects FOXE1 transcription. DNA-binding assays demonstrated that, exclusively, the sequence containing the A allele recruited the USF1/USF2 transcription factors, while both alleles formed a complex in which DREAM/CREB/αCREM participated. Transfection studies showed an allele-dependent transcriptional regulation of FOXE1. We propose a FOXE1 regulation model dependent on the rs1867277 genotype, indicating that this SNP is a causal variant in thyroid cancer susceptibility. Our results constitute the first functional explanation for an association identified by a GWAS and thereby elucidate a mechanism of thyroid cancer susceptibility. They also attest to the efficacy of candidate gene approaches in the GWAS era

There is No Distinctive Gut Microbiota Signature in the Metabolic Syndrome: Contribution of Cardiovascular Disease Risk Factors and Associated Medication

© 2020 by the authors.The gut microbiota (GM) has attracted attention as a new target to combat several diseases, including metabolic syndrome (MetS), a pathological condition with many factors (diabetes, obesity, dyslipidemia, hypertension, etc.) that increase cardiovascular disease (CVD) risk. However, the existence of a characteristic taxonomic signature associated with obesity-related metabolic dysfunctions is under debate. To investigate the contribution of the CVD risk factors and(or) their associated drug treatments in the composition and functionality of GM in MetS patients, we compared the GM of obese individuals (n = 69) vs. MetS patients (n = 50), as well as within patients, depending on their treatments. We also explored associations between medication, GM, clinical variables, endotoxemia, and short-chain fatty acids. Poly-drug treatments, conventional in MetS patients, prevented the accurate association between medication and GM profiles. Our results highlight the heterogeneity of taxonomic signatures in MetS patients, which mainly depend on the CVD risk factors. Hypertension and(or) its associated medication was the primary trait involved in the shaping of GM, with an overabundance of lipopolysaccharide-producing microbial groups from the Proteobacteria phylum. In the context of precision medicine, our results highlight that targeting GM to prevent and(or) treat MetS should consider MetS patients more individually, according to their CVD risk factors and associated medication.This research was funded by MINECO (Spain), grant number AGL2015-64124-R, and Fundación Séneca de la Región de Murcia (Spain), grant number 20880/PI/18. A.C.M. is the holder of a predoctoral grant from MINECO (Spain).Peer reviewe

La figura de la enfermera educadora hospitalaria mejora la HbA1c y el perfil lipídico de los pacientes con diabetes tipo 1

La educación diabetológica ha demostrado ser esencial en la atención del paciente diabético. Para realizar esta tarea educacional, la Unidad de Diabetes del Área VII Murcia Este, que incorporó a enfermeras especializadas en educación diabetológica avanzada en el Hospital General Universitario Reina Sofía de Murcia. Se realizó un estudio retrospectivo, donde se valoró la actuación de dichas enfermeras mediante la evaluación de los pacientes diabéticos tipo 1 que acudieron a sus consultas entre los años 2007 y 2011. Se analizaron un total de 179 historias clínicas de pacientes con diabetes mellitus tipo 1 (DM1) mayores de 11 años, siendo 103 (52,3%) varones y 94 (47,7%) mujeres. Los pacientes presentaban una edad media de 38.25 ± 14.02 años y un tiempo de duración de la diabetes medio de 16,22 ± 11,73 años. El valor de HbA1c inicial medio fue de 8,49 ± 2,04%. De los 197 pacientes, solo 37 (16,2%) eran menores de 25 años en el momento de acudir a consulta. Los resultados obtenidos demostraron que la disminución de la HbA1c (-0,57 ± 1,80%) era significativa a los 6 meses (p: 0,002) de la primera consulta alcanzando valores de 7,86 ± 1,39 y manteniéndose a partir de ese momento. Las dosis de insulina fueron estables a lo largo del estudio

Psychoeducative groups help control type 2 diabetes in a primary care setting

Introduction: The purpose of this study is to measure the impact of a psychoeducational group intervention in diabetes using glycosylated haemoglobin (HbA1c), the body mass index (BMI) and cardiovascular risk factors (CVRF) compared with conventional educational measures provided individually. Methods: A quasi-experimental study (pre/post-intervention) with a non-equivalent control group was conducted, including 72 type 2 individuals with diabetes (mean data: age 63.08 years, HbA1C 6.98%, BMI 30.48 kg/m²). The beneficial effect of psychoeducational group therapy in the study group (PGT) was compared with conventional diabetes education in the control group (CG). Results: The PGT had a higher mean HbA1c reduction (-0.51 ± 1.7 vs. -0.06 ± 0.53%, p 0.003), met the objectives of optimal control of HbA1c to a higher degree (80% vs. 48%, p 0.005) and greater mean weight reduction (-1.93 ± 3.57 vs. 0.52 ± 1.73 kg, p 0002) than the CG.A significant improvement in total cholesterol, LDL cholesterol, triglycerides, systolic and diastolic blood pressure was achieved in PGT (all p < 0.05). Conclusions: PGT patients achieved a significant improvement in HbA1C, BMI and CVRF, and outperformed the conventional diabetes education group in achieving the optimal diabetes control objectives. Structural changes in the assistance programs should be considered to introduce these more efficient therapies for diabetes education in primary care

PheoSeq : A Targeted Next-Generation Sequencing Assay for Pheochromocytoma and Paraganglioma Diagnostics

Genetic diagnosis is recommended for all pheochromocytoma and paraganglioma (PPGL) cases, as driver mutations are identified in approximately 80% of the cases. As the list of related genes expands, genetic diagnosis becomes more time-consuming, and targeted next-generation sequencing (NGS) has emerged as a cost-effective tool. This study aimed to optimize targeted NGS in PPGL genetic diagnostics. A workflow based on two customized targeted NGS assays was validated to study the 18 main PPGL genes in germline and frozen tumor DNA, with one of them specifically directed toward formalin-fixed paraffin-embedded tissue. The series involved 453 unrelated PPGL patients, of whom 30 had known mutations and were used as controls. Partial screening using Sanger had been performed in 275 patients. NGS results were complemented with the study of gross deletions. NGS assay showed a sensitivity ≥99.4%, regardless of DNA source. We identified 45 variants of unknown significance and 89 pathogenic mutations, the latter being germline in 29 (7.2%) and somatic in 58 (31.7%) of the 183 tumors studied. In 37 patients previously studied by Sanger sequencing, the causal mutation could be identified. We demonstrated that both assays are an efficient and accurate alternative to conventional sequencing. Their application facilitates the study of minor PPGL genes, and enables genetic diagnoses in patients with incongruent or missing clinical data, who would otherwise be missed