BackgroundA large number of studies have investigated whether polymorphisms in the Toll-like receptor (TLR) genes are implicated in susceptibility to tuberculosis (TB) in different populations. However, the results are inconsistent and inconclusive.MethodsA literature search was conducted using the PubMed, EMBASE, Medline (Ovid), ISI Web of Knowledge and Chinese National Knowledge Infrastructure (CNKI). A meta-analysis on the associations between the TLR1 G1805T, TLR2 T597C, T1350C, G2258A, and TLR6 C745T polymorphisms and TB risk was carried out by comparison using different genetic models.ResultsIn total, 16 studies from 14 articles were included in this review. In meta-analysis, significant associations were observed between the TLR2 2258AA (AA vs. AG+AG, OR 5.82, 95% CI 1.30–26.16, P = 0.02) and TLR6 745TT (TT vs. CT+CC, OR 0.61, 95% CI 0.39–0.97, P = 0.04) polymorphisms and TB risk. In the subgroup analysis by ethnicity, Africans and American Hispanic subjects with the TLR1 1805T allele had an increased susceptibility, whereas Asian and European subjects with the TLR2 2258A allele had an increased susceptibility to TB.ConclusionsThe meta-analysis indicated that TLR2 G2258A is associated with increased TB risk, especially in Asians and Europeans. TLR1 G1805T is associated with increased TB in Africans and American Hispanics. TLR6 C745T is associated with decreased TB risk. Our systematic review and meta-analysis reported an interesting preliminary conclusion, but this must be validated by future large-scale and functional studies in different populations.

BackgroundThe present study aimed to investigate the genetic polymorphisms in exon 4 of the NOD2 gene in tuberculosis patients and healthy controls, in order to clarify whether polymorphisms in the NOD2 gene is associated with tuberculosis.MethodsA case-control study was performed on the Chinese Han, Uygur and Kazak populations. Exon 4 of the NOD2 gene was sequenced in 425 TB patients and 380 healthy controls to identify SNPs.ResultsThe frequency of T/G genotypes for the Arg587Arg (CGT → CGG) single nucleotide polymorphism (SNP) in NOD2 was found to be significantly higher in the Uygur (34.9%) and Kazak (37.1%) populations than the Han population (18.6%). Also, the frequency of G/G genotypes for the Arg587Arg SNP was significantly higher in the Uyghur (8.3%) and Kazak (5.4%) populations than the Han population (0.9%). Meanwhile, no significant difference was found in the Arg587Arg polymorphism between the tuberculosis patients and healthy controls in the Uyghur and Kazak populations (P > 0.05) whereas, a significant difference was observed in the Arg587Arg polymorphism between the tuberculosis patients and healthy controls in the Han population (P < 0.01). The odd ratio of 2.16 (95% CI = 1.31-3.58; P < 0.01) indicated that the Arg587Arg SNP in NOD2 may be associated with susceptibility to tuberculosis in the Chinese Han population.ConclusionsOur study is the first to demonstrate that the Arg587Arg SNP in NOD2 is a new possible risk factor for tuberculosis in the Chinese Han population, but not in the Uyghur and Kazak populations. Our results may reflect racial differences in genetic susceptibility to tuberculosis.

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Previous studies have indicated the important role of block of proliferation 1 (BOP1) in the progression of several malignant tumors; no comprehensive pan-cancer analysis of BOP1 has been performed. Here, we aim to systematically identify the expression, prognostic value, and potential immunological functions of BOP1 in 33 malignancies. We obtained the gene expression data and clinical information from multiple public databases to assess the expression level and prognostic value of BOP1 in 33 cancers. We also analyzed the relationship between BOP1 expression and DNA methylation, tumor microenvironment (TME), microsatellite instability (MSI), tumor mutational burden (TMB), and immune checkpoints. Moreover, we conducted gene set enrichment analysis (GSEA) to investigate the biological function and signal transduction pathways of BOP1 in different types of tumors. Finally, we validated the expression of BOP1 in lung cancer cell line and detected the influence of BOP1 on lung cancer cell migration and the expression of epithelial-mesenchymal transition- (EMT-) related genes. Collectively, our findings elucidated that BOP1 has the potential to be a promising molecular prognostic biomarker for predicting poor survival in various malignant tumors, as well as a cancer-promoting gene involved in tumorigenesis and tumor immunity.