RESUMEN
In this study, we investigated the correlation between the JAK2V617F mutation and thrombosis in patients with myeloproliferative neoplasm (MPN) using real-time fluorescence quantitative PCR. The incidence of thrombus was monitored and blood and coagulation were routinely assayed in patients with MPN. The JAK2V617F mutation was found in 8/68 individuals in the control group (11.8%); it was expressed in 44/68 patients with MPN (64.7%), suggesting that the rate of this mutation was significantly higher in patients with MPN than that in the control group. Twenty-six MPN patients (38.2%) showed symptoms of thrombosis; MPN patients with thrombosis showed a significantly higher rate of the JAK2V617F mutation, were of a greater age, and had higher blood pressure than MPN patients without thrombosis. In addition, the white blood cells (WBC) (21.98 ± 1.95) and platelets (364.68 ± 97.72) were significantly higher in patients, expressing the mutated gene, with polycythemia vera than in the patients without the mutation. The WBC (32.89 ± 4.25) and hemoglobin (161.92 ± 16.19) were significantly increased in the essential thrombocythemia patients with gene mutation compared with the patients without mutation. MPN patients showed higher blood clotting ability than the control subjects; moreover, MPN patients with the JAK2V617F mutation showed higher blood clotting ability than those without the mutation. The findings of this study indicate that the JAK2V617F mutation is correlated with the incidence of thrombosis, and analysis of this mutation has important clinical significance in the diagnosis and treatment of MPN.
Asunto(s)
Janus Quinasa 2/genética , Mutación , Policitemia Vera/genética , Mielofibrosis Primaria/genética , Trombocitemia Esencial/genética , Trombosis/genética , Adulto , Factores de Edad , Anciano , Sustitución de Aminoácidos , Presión Sanguínea , Estudios de Casos y Controles , Femenino , Fluorescencia , Expresión Génica , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Recuento de Plaquetas , Policitemia Vera/complicaciones , Policitemia Vera/diagnóstico , Policitemia Vera/patología , Mielofibrosis Primaria/complicaciones , Mielofibrosis Primaria/diagnóstico , Mielofibrosis Primaria/patología , Reacción en Cadena en Tiempo Real de la Polimerasa , Trombocitemia Esencial/complicaciones , Trombocitemia Esencial/diagnóstico , Trombocitemia Esencial/patología , Trombosis/complicaciones , Trombosis/diagnóstico , Trombosis/patologíaRESUMEN
Tumor necrosis factor superfamily member 4 (TNFSF4) plays an important role in atherosclerosis development. However, the biological significance of TNFSF4 variants on myocardial infarction (MI) pathogenesis remains poorly understood. We investigated the influence of 5 TNFSF4 tagging single nucleotide polymorphisms (rs3861950, rs17346501, rs7518045, rs1234313, and rs3850641) on individual susceptibility to MI in a Chinese population of 285 MI patients and 645 controls. Genotyping was performed using the polymerase chain reaction-ligase detection reaction method. In multivariate logistic regression analysis, only the TNFSF4 tagging single nucleotide polymorphism rs7518045 exhibited a significant effect on MI risk; A allele (odds ratio = 0.68, 95% confidence interval = 0.46-1.00, P = 0.048) and AA genotype (odds ratio = 0.64, 95% confidence interval = 0.42-0.97, P = 0.036) were associated with a decreased risk of MI compared with the G allele and the combined AG/GG genotype, respectively. Moreover, the haplotype rs3861950C-rs17346501C-rs7518045A-rs1234313G containing the rs7518045 A allele also exhibited a significant association with a decreased risk for MI (odds ratio = 0.42, 95% confidence interval = 0.21-0.84, P = 0.011). Our study showed that the A allele of the rs7518045 and haplotype rs3861950C-rs17346501C-rs7518045A-rs1234313G in the TNFSF4 gene were associated with decreased MI risk in a Chinese Han population. Further studies using larger sample sizes and in diverse ethnic populations are needed to confirm the general validity of our findings.
Asunto(s)
Pueblo Asiatico/etnología , Pueblo Asiatico/genética , Infarto del Miocardio/genética , Ligando OX40/genética , Polimorfismo de Nucleótido Simple , Anciano , Estudios de Casos y Controles , China/etnología , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/etnologíaRESUMEN
A mouse model of acute lung injury (ALI) was chosen in this study to explore the key genes and pathways involved in the process of ALI with microarray technology. Gene expression microarray data were downloaded from the Gene Expression Omnibus database. Mice from the experimental group were further divided into 6 subgroups, which received octadecenoate treatments for 1, 1.5, 3, 4, 18, and 24 h. Differentially co-expressed genes were screened to uncover the pathogenesis of ALI. Almost all of the differentially co-expressed genes were identified at two times: 1.5 and 3 h. Functional analysis revealed that several inflammation-related pathways were significantly enriched. Ubiquitin-mediated proteolysis, hematopoietic cell lineage, and leukocyte transendothelial migration were enriched at 1.5 h. The B cell receptor signaling pathway, T cell receptor signaling pathway, natural killer cell-mediated cytotoxicity, Fc epsilon RI signaling pathway, and ubiquitin-mediated proteolysis were significantly enriched at 3 h. It could be inferred that ALI initiated at 1.5 h and lasted through 3 h. However, co-expression patterns were not found from 4 h onward. In conclusion, several key genes and pathways implicated in the development of ALI were found in this study using the mouse model, among which ubiquitin-mediated proteolysis appears to play an important role in the process.