Genetic variants in MARCO are associated with the susceptibility to pulmonary tuberculosis in Chinese Han population.

BACKGROUND: Susceptibility to tuberculosis is not only determined by Mycobacterium tuberculosis infection, but also by the genetic component of the host. Macrophage receptor with a collagenous structure (MARCO) is essential components required for toll like receptor-signaling in macrophage response to Mycobacterium tuberculosis, which may contribute to tuberculosis risk. PRINCIPAL FINDINGS: To specifically investigated whether single nucleotide polymorphisms (SNPs) in MARCO gene are associated with pulmonary tuberculosis in Chinese Han population. By selecting tagging SNPs in MARCO gene, 17 tag SNPs were identified and genotyped in 923 pulmonary tuberculosis patients and 1033 healthy control subjects using a hospital based case-control association study. Single-point and haplotype analysis revealed an association in intron and exon region of MARCO gene. One SNP (rs17009726) was associated with susceptibility to pulmonary tuberculosis, where the carriers of the G allele had a 1.65 fold (95% CI = 1.32-2.05, p(corrected) = 9.27E-5) increased risk of pulmonary tuberculosis. Haplotype analysis revealed that haplotype GC containing G allele of 17009726 and haplotype TGCC (rs17795618T/A, rs1371562G/T, rs6761637T/C, rs2011839C/T) were also associated with susceptibility to pulmonary tuberculosis (p(corrected) = 0.0001 and 0.029, respectively). CONCLUSIONS: Our study suggested that genetic variants in MARCO gene were associated with pulmonary tuberculosis susceptibility in Chinese Han population, and the findings emphasize the importance of MARCO mediated immune responses in the pathogenesis of tuberculosis.

Toll-like receptors, tumor necrosis factor-α, and interleukin-10 gene polymorphisms in risk of pulmonary tuberculosis and disease severity.

Toll-like receptors (TLRs) and cytokines play key roles in innate and adaptive immunity against Mycobacterium tuberculosis (M.TB). The aim of this study was to investigate whether the functional genetic variations at position 1805 G/T in TLR1, 2258 A/G in TLR2, -857 C/T, and -863 A/C in tumor necrosis factor-α (TNF-α), as well as -819 C/T in interleukin-10 (IL-10) confer susceptibility to pulmonary tuberculosis (PTB). We performed a hospital-based case-control study using 543 case patients and 544 controls. Multivariate logistic regression analysis revealed that the TT genotype of -857 C/T in TNF-α gene was significantly associated with lower risk of PTB, in comparison with other genotypes (odds ratios [OR] = 0.68, 95% confidence interval [CI] = 0.53-0.86, p = 0.001). Conversely, the genetic variants of -863 A/C in TNF-α gene was associated with susceptibility to PTB (OR = 2.42%, 95% CI = 1.28-4.59, p = 0.007) and clinical severity of disease (OR = 3.59%, 95% CI = 1.41-9.11, p = 0.007). Our results indicated that the variants in TNF-α gene were associated with susceptibility to PTB and clinical severity of disease, whereas no significance could be inferred from TLRs and IL-10 genes polymorphisms.