RESUMO
Although epidemiological evidence suggests a human genetic basis of pulmonary tuberculosis (PTB) susceptibility, the identification of specific genes and alleles influencing PTB risk has proven to be difficult. Previous genome-wide association (GWA) studies have identified only three novel loci with modest effect sizes in sub-Saharan African and Russian populations. We performed a GWA study of 550,352 autosomal SNPs in a family-based discovery Moroccan sample (on the full population and on the subset with PTB diagnosis at <25 years), which identified 143 SNPs with p < 1 × 10(-4). The replication study in an independent case/control sample identified four SNPs displaying a p < 0.01 implicating the same risk allele. In the combined sample including 556 PTB subjects and 650 controls these four SNPs showed suggestive association (2 × 10(-6) < p < 4 × 10(-5)): rs358793 and rs17590261 were intergenic, while rs6786408 and rs916943 were located in introns of FOXP1 and AGMO, respectively. Both genes are involved in the function of macrophages, which are the site of latency and reactivation of Mycobacterium tuberculosis. The most significant finding (p = 2 × 10(-6)) was obtained for the AGMO SNP in an early (<25 years) age-at-onset subset, confirming the importance of considering age-at-onset to decipher the genetic basis of PTB. Although only suggestive, these findings highlight several avenues for future research in the human genetics of PTB.
Assuntos
Estudo de Associação Genômica Ampla , Tuberculose Pulmonar/genética , Adolescente , Adulto , Idade de Início , Idoso , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Loci Gênicos , Técnicas de Genotipagem , Humanos , Lactente , Íntrons , Masculino , Pessoa de Meia-Idade , Oxigenases de Função Mista/genética , Oxigenases de Função Mista/metabolismo , Marrocos , Mycobacterium tuberculosis , Polimorfismo de Nucleotídeo Único , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Reprodutibilidade dos Testes , Fatores de Risco , Tuberculose Pulmonar/microbiologia , Adulto JovemRESUMO
Since the advent of antituberculosis drugs, endobronchial tuberculosis has become an exceptional finding, often in a misleading context. Cases reported generally occur in patients with immune deficit. We report 21 cases of endobronchial tuberculosis in immunocompetent patients (mean age 37 years). Clinical and radiological signs were not specific. Bronchial fibroscopy was essential for certain diagnosis, particularly in budding forms. Early treatment reduced the risk of complications. Based on our experience with these 21 cases, we propose a discussion of the pathogenic mechanisms involved and the diagnostic difficulties encountered as well as the disease course and risk of complications that can be expected.
