RESUMO
It is generally believed that susceptibility to both organ-specific and systemic autoimmune diseases is under polygenic control. Although multiple genes have been implicated in each type of autoimmune disease, few are known to have a significant impact on both. Here, we investigated the significance of polymorphisms in the human gene CD24 and the susceptibility to multiple sclerosis (MS) and systemic lupus erythematosus (SLE). We used cases/control studies to determine the association between CD24 polymorphism and the risk of MS and SLE. In addition, we also considered transmission disequilibrium tests using family data from two cohorts consisting of a total of 150 pedigrees of MS families and 187 pedigrees of SLE families. Our analyses revealed that a dinucleotide deletion at position 1527 approximately 1528 (P1527(del)) from the CD24 mRNA translation start site is associated with a significantly reduced risk (odds ratio = 0.54 with 95% confidence interval = 0.34-0.82) and delayed progression (p = 0.0188) of MS. Among the SLE cohort, we found a similar reduction of risk with the same polymorphism (odds ratio = 0.38, confidence interval = 0.22-0.62). More importantly, using 150 pedigrees of MS families from two independent cohorts and the TRANSMIT software, we found that the P1527(del) allele was preferentially transmitted to unaffected individuals (p = 0.002). Likewise, an analysis of 187 SLE families revealed the dinucleotide-deleted allele was preferentially transmitted to unaffected individuals (p = 0.002). The mRNA levels for the dinucleotide-deletion allele were 2.5-fold less than that of the wild-type allele. The dinucleotide deletion significantly reduced the stability of CD24 mRNA. Our results demonstrate that a destabilizing dinucleotide deletion in the 3' UTR of CD24 mRNA conveys significant protection against both MS and SLE.
Assuntos
Antígeno CD24/genética , Repetições de Dinucleotídeos/genética , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/prevenção & controle , Esclerose Múltipla/genética , Esclerose Múltipla/prevenção & controle , Deleção de Sequência/genética , Regiões 3' não Traduzidas/genética , Alelos , Animais , Antígeno CD24/imunologia , Antígeno CD24/metabolismo , Células CHO , Estudos de Casos e Controles , Cromossomos Humanos/genética , Cricetinae , Cricetulus , Progressão da Doença , Feminino , Regulação da Expressão Gênica , Predisposição Genética para Doença , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Polimorfismo de Nucleotídeo Único/genética , Estabilidade de RNA/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de RiscoRESUMO
Brain tumors, particularly malignant gliomas, have a high incidence of venous thromboembolism (VTE), but current guidelines do not support primary VTE prophylaxis for ambulatory patients with brain tumors. The often subtle presentation of VTE warrants increased vigilance for early diagnosis and treatment. This article presents a case study of a patient with VTE and offers suggestions for future research.