RESUMEN
The data presented in this article are related to the research article entitled "The autoimmune risk gene ZMIZ1 is a vitamin D responsived marker of a molecular phenotype of multiple sclerosis" Fewings et al. (2017) [1]. Here we identify the set of genes correlated with ZMIZ1 in multiple cohorts, provide phenotypic details on those cohorts, and identify the genes negatively correlated with ZMIZ1 and the cells predominantly expressing those genes. We identify the metabolic pathways in which the molecular phenotype genes are over-represented. Finally, we present the flow cytometry gating strategy we have used to identify the immune cells from blood which are producing ZMIZ1 and RPS6.
RESUMEN
Multiple Sclerosis (MS) is a neurological condition driven in part by immune cells from the peripheral circulation, the targets for current successful therapies. The autoimmune and MS risk gene ZMIZ1 is underexpressed in blood in people with MS. We show that, from three independent sets of transcriptomic data, expression of ZMIZ1 is tightly correlated with that of hundreds of other genes. Further we show expression is partially heritable (heritability 0.26), relatively stable over time, predominantly in plasmacytoid dendritic cells and non-classical monocytes, and that levels of ZMIZ1 protein expression are reduced in MS. ZMIZ1 gene expression is increased in response to calcipotriol (1,25 Vitamin D3) (p < 0.0003) and associated with Epstein Barr Virus (EBV) EBNA-1 antibody titre (p < 0.004). MS therapies fingolimod and dimethyl fumarate altered blood ZMIZ1 gene expression compared to untreated MS. The phenotype indicates susceptibility to MS, and may correspond with clinical response and represent a novel clinical target.
Asunto(s)
Autoinmunidad/genética , Esclerosis Múltiple/etiología , Esclerosis Múltiple/metabolismo , Fenotipo , Factores de Transcripción/genética , Vitamina D/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Estudios de Casos y Controles , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Susceptibilidad a Enfermedades , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/inmunología , Femenino , Perfilación de la Expresión Génica , Regulación de la Expresión Génica , Genotipo , Herpesvirus Humano 4/inmunología , Humanos , Patrón de Herencia , Masculino , Persona de Mediana Edad , Monocitos/inmunología , Monocitos/metabolismo , Esclerosis Múltiple/patología , Polimorfismo de Nucleótido Simple , Estaciones del Año , Factores de Transcripción/metabolismo , Vitamina D/farmacología , Adulto JovenRESUMEN
Following a complex research and development process last year that led to the drafting of a comprehensive health care reform proposal, President Bill Clinton presented the U.S. Congress and the nation with an outline for reform in September, and followed up with a detailed plan and with a reform bill in October. Now it's Congress' turn to respond. Hospitals & Health Networks' senior editor Renee Blankenau interviewed 11 members of Congress whose views represent a broad spectrum of congressional opinion. What version of federal reform will emerge this year? These legislators have the inside track.
Asunto(s)
Reforma de la Atención de Salud/legislación & jurisprudencia , Predicción , Formulación de Políticas , Política , Estados UnidosRESUMEN
Senator Nickles (R-Okla) was interviewed in March in his Oklahoma City office on the 18th floor of the Liberty Bank Building. The interview was shortened by a late start and because the Senator was on his way to an editorial meeting of the Daily Oklahoman. Nonetheless, Senator Nickles, a young and energetic man in his early forties, was relaxed and in no apparent rush. Nickles, still the youngest Senator in Washington, has been a US Senator for 11 years. Because of the combination of youth and promise of long tenure, he is considered to be a rising power in the Senate. He is a conservative and a philosophical ally of medicine.