RESUMO
Toll-like receptors (TLRs) are key sensors of mycobacterial infections and play a crucial role in the initiation and coordination of the antimycobacterial innate immune response. T1805G, a functional TLR1 single nucleotide polymorphism (SNP), has been associated with susceptibility to pulmonary tuberculosis (PTB), but contradictory results among different populations have been reported. Our objective was to study this SNP in a genetically homogeneous population to evaluate its role in conferring susceptibility or resistance to PTB. In our population, the 1805G allele and the GG genotype (OR 2.04, 95%CI 1.26-3.31) influence susceptibility to PTB, in contrast with data observed in other populations.
Assuntos
Polimorfismo de Nucleotídeo Único , Receptor 1 Toll-Like/genética , Tuberculose Pulmonar/genética , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Frequência do Gene , Predisposição Genética para Doença , Humanos , Razão de Chances , Fenótipo , Reação em Cadeia da Polimerase , Fatores de Risco , Espanha , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/microbiologiaRESUMO
OBJECTIVE: To study whether two functional single nucleotide polymorphisms of the CC chemokine ligand 5 (CCL5) gene could affect susceptibility to pulmonary tuberculosis (TB) in a human immunodeficiency virus negative genetically homogeneous population, containing newly diagnosed patients with active disease. DESIGN: Seventy-six patients with active pulmonary TB (PTB) and 157 healthy control subjects from Cantabria, northern Spain, were genotyped for the CCL5 -403G/A and -28C/G polymorphisms. RESULTS: The frequency of the CCL5-403G/A and -28C/G promoter polymorphisms were significantly different between patients with active TB and control subjects. Three of the four possible haplotypes were also significantly different. The G/G-C/C diplotype was much more frequent in the healthy control group and the G/G-G/G and A/A-C/C diplotypes were more frequent in patients with PTB. CONCLUSION: Our findings indicate that CCL5 may play a role in conferring susceptibility to active PTB. Thus, the -403G and -28C alleles, either separately or combined in the G-C haplotype and the GG/CC diplotype, may be related to protection against PTB. By contrast, the -403A and -28G alleles, the G-G or A-C haplotypes and the G/G-G/G and A/A-C/C diplotypes may confer susceptibility to PTB.