Asunto(s)
Médula Ósea/patología , Antígeno CD56/metabolismo , Células Dendríticas/patología , Neoplasias Hematológicas/metabolismo , Neoplasias Cutáneas/metabolismo , Anciano , Antígenos CD4/metabolismo , Neoplasias Hematológicas/patología , Humanos , Subunidad alfa del Receptor de Interleucina-3/metabolismo , Masculino , Fenotipo , Neoplasias Cutáneas/patologíaAsunto(s)
Transformación Celular Neoplásica/patología , Leucemia Linfocítica Crónica de Células B/diagnóstico , Leucemia Linfocítica Crónica de Células B/patología , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/patología , Enfermedades del Pene/diagnóstico , Enfermedades del Pene/patología , Neoplasias del Pene/diagnóstico , Neoplasias del Pene/patología , Úlcera Cutánea/diagnóstico , Úlcera Cutánea/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Transformación Celular Neoplásica/efectos de los fármacos , Humanos , Leucemia Linfocítica Crónica de Células B/tratamiento farmacológico , Ganglios Linfáticos/efectos de los fármacos , Ganglios Linfáticos/patología , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Masculino , Enfermedades del Pene/tratamiento farmacológico , Neoplasias del Pene/tratamiento farmacológico , Pene/patología , Úlcera Cutánea/tratamiento farmacológicoRESUMEN
Alopecia areata (AA) is a prevalent autoimmune disease with 10 known susceptibility loci. Here we perform the first meta-analysis of research on AA by combining data from two genome-wide association studies (GWAS), and replication with supplemented ImmunoChip data for a total of 3,253 cases and 7,543 controls. The strongest region of association is the major histocompatibility complex, where we fine-map four independent effects, all implicating human leukocyte antigen-DR as a key aetiologic driver. Outside the major histocompatibility complex, we identify two novel loci that exceed the threshold of statistical significance, containing ACOXL/BCL2L11(BIM) (2q13); GARP (LRRC32) (11q13.5), as well as a third nominally significant region SH2B3(LNK)/ATXN2 (12q24.12). Candidate susceptibility gene expression analysis in these regions demonstrates expression in relevant immune cells and the hair follicle. We integrate our results with data from seven other autoimmune diseases and provide insight into the alignment of AA within these disorders. Our findings uncover new molecular pathways disrupted in AA, including autophagy/apoptosis, transforming growth factor beta/Tregs and JAK kinase signalling, and support the causal role of aberrant immune processes in AA.
Asunto(s)
Alopecia Areata/genética , Proteínas Reguladoras de la Apoptosis/genética , Ataxina-2/genética , Predisposición Genética a la Enfermedad , Antígenos HLA/genética , Proteínas de la Membrana/genética , Polimorfismo de Nucleótido Simple , Proteínas/genética , Proteínas Proto-Oncogénicas/genética , Proteínas Adaptadoras Transductoras de Señales , Alelos , Animales , Proteína 11 Similar a Bcl2 , Estudios de Casos y Controles , Femenino , Estudio de Asociación del Genoma Completo , Humanos , Péptidos y Proteínas de Señalización Intracelular , Masculino , Ratones , Microscopía Fluorescente , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Análisis de Componente Principal , Conformación Proteica , Piel/metabolismoRESUMEN
Obesity affects a disproportionate proportion of total knee arthroplasty (TKA) patients. Our study explores pre-operative characteristics between obese and non-obese patients undergoing TKA surgery. A cohort of 4718 osteoarthritic patients, undergoing primary TKA, was studied. Patients were stratified according to BMI classes. Each class was compared in terms of age, race, gender, level of education, insurance status, pre-operative WOMAC, SF-36, and Elixhauser comorbidities. There was a positive relationship between BMI and female gender, non-white race, Medicaid, private insurance, and self-pay. A negative relationship was observed between BMI and age, Medicare, WOMAC and SF-36. Obese TKA candidates differ from their non-obese counterparts in a number of demographic, socioeconomic, and clinical characteristics.