RESUMEN
Background: Post-TIPS hepatic encephalopathy (PSE) is a complex process involving numerous risk factors; the root cause is unclear, but an elevation of blood ammonia due to portosystemic shunt and metabolic disorders in hepatocytes has been proposed as an important risk factor. Aims: The aim of this study was to investigate the impact of pathological features of mitochondrial ultrastructure on PSE via transjugular liver biopsy at TIPS implantation. Methods: We evaluated the pathological damage of mitochondrial ultrastructure on recruited patients by the Flameng classification system. A score ≤2 (no or low damage) was defined as group A, and a score >2 (high damage level) was defined as group B; routine follow-up was required at 1 and 2 years; the incidence of PSE and multiple clinical data were recorded. Results: A total of 78 cases in group A and 42 in group B completed the study. The incidence of PSE after 1 and 2 years in group B (35.7% and 45.2%, respectively) was significantly higher than that in group A (16.7% and 24.4%, respectively); the 1- and 2-year OR (95% CI) were 2.778 (1.166-6.615) and 2.565 (1.155-5.696), respectively, for groups A and B. Importantly, group B had worse incidence of PSE than group A [P=0.014, hazard ratio (95%CI): 2.172 (1.190-4.678)]. Conclusion: Aggressive damage to mitochondrial ultrastructure in liver shunt predicts susceptibility to PSE. The registration number is NCT02540382.
Asunto(s)
Susceptibilidad a Enfermedades/patología , Encefalopatía Hepática/cirugía , Hipertensión Portal/cirugía , Cirrosis Hepática/cirugía , Mitocondrias/ultraestructura , Derivación Portosistémica Intrahepática Transyugular/efectos adversos , Adulto , Anciano , Biopsia con Aguja , Estudios de Cohortes , Várices Esofágicas y Gástricas/complicaciones , Várices Esofágicas y Gástricas/patología , Femenino , Encefalopatía Hepática/etiología , Encefalopatía Hepática/patología , Humanos , Hipertensión Portal/complicaciones , Hipertensión Portal/patología , Inmunohistoquímica , Hígado/patología , Hígado/ultraestructura , Cirrosis Hepática/complicaciones , Cirrosis Hepática/patología , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos , Medición de Riesgo , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
OBJECTIVES: Previous association studies have identified genetic variants in the human leukocyte antigen (HLA) complex as substantial risk factors for idiopathic inflammatory myopathies (IIMs). However, a great number of genes are located in the HLA region, and thus fine mapping is quite necessary. METHODS: Targeted capture sequencing were performed on the whole HLA region in 42 IIM patients and 24 healthy controls. A microarray analysis was applied to analyze gene expression profiles in additional 20 newly diagnosed IIM and five healthy controls. RESULTS: The HLA region was confirmed to be associated with IIMs in Chinese patients. By gene expression profiling and pathway analysis, several genes were identified as candidates for IIM risk factors, including HLA-A, HLA-B, HLA-DRB5, HLA-DRB1, HLA-DQA1, HLA-DQB1 and HLA-DQB2. Interestingly, p.Y107V of the HLA-DRB1 was predicted to be a potential causal non-synonymous variation for IIMs that may affect the antigen-binding groove of the HLA-II molecule. CONCLUSIONS: Our data have revealed novel genetic variations in the HLA region of IIM patients and provide new insight into the pathogenesis and diagnosis of IIMs.
Asunto(s)
Perfilación de la Expresión Génica/métodos , Variación Genética , Antígenos HLA/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Miositis/genética , Análisis de Secuencia por Matrices de Oligonucleótidos , Adulto , Pueblo Asiatico/genética , Estudios de Casos y Controles , China/epidemiología , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Antígenos HLA/inmunología , Humanos , Masculino , Persona de Mediana Edad , Miositis/diagnóstico , Miositis/etnología , Miositis/inmunología , Fenotipo , Valor Predictivo de las Pruebas , Factores de Riesgo , TranscriptomaRESUMEN
There is considerable worldwide interest in identifying genes related to susceptibility to asthma. Progress has been slow in part because of the complexity and heterogeneity of the disease. Although at least 170 genes located on 10 chromosomes have been associated with or in linkage with asthma and asthma-related phenotypes, the majority of the reports have either been preliminary or the results have been controversial. In order to overcome the problems with the inherent complexity of asthma and methodological issues, the authors propose a strategy for identification of asthma susceptibility genes based on theories of systems biology and bioinformatics and candidate gene approach.