Integrated analyses reveal hsa_circ_0028883 as a diagnostic biomarker in active tuberculosis.

Circular RNAs (circRNAs) are known to be closely involved in various diseases progression. Nevertheless, their function and underlying mechanisms in tuberculosis (TB) remain largely unknown. The aim of the present study was to explore their potential diagnostic values in TB. We downloaded the gene expression datasets of circRNA (GSE117563 and GSE106953), microRNA (miRNA, dataset GSE29190) and mRNA (GSE54992) from Gene Expression Omnibus (GEO) database. A competing endogenous RNAs (ceRNA) network was constructed based on circRNA-miRNA-mRNA potential interaction. We also constructed a circRNA-miRNA-hub gene regulatory module by using the Cytohubba. Gene ontology (GO) as well as Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were used to predict their biological functions. By further validation, the expression level of hsa_circ_0028883 and hsa-miR-409-5p were detected by qRT-PCR in 20 active TB patients and 20 healthy donors. Then, Receiver Operating Characteristic (ROC) was constructed to evaluate the diagnostic values of hsa_circ_0028883. 1 differentially expressed circRNA (DE-circRNA), 1 differentially expressed miRNA (DE-miRNA), and 44 differentially expressed mRNAs (DE-mRNAs) were selected for the construction of ceRNA network in TB. A circRNA-miRNA-hub gene (mRNA) sub-network was constructed based on 1 DE-circRNA, 1 DE-miRNA, and 8 DE-mRNAs. Hsa_circ_0028883/hsa-miR-409-5p/mRNA interactions may provide some novel mechanisms for active TB. GO and KEGG pathway analysis indicated the possible function of hsa_circ_0028883 with TB. ROC analysis revealed that hsa_circ_0028883 had potential value for TB diagnosis. Hsa_circ_0028883 is a potentially reliable biomarker to diagnose active TB, but there remains a need to further study the mechanism in TB.

Association of IFNGR1 and IFNG genetic polymorphisms with the risk for pulmonary tuberculosis in the Chinese Tibetan population.

Interferon-gamma (IFNG) and its receptor (IFNGR1) are principal genes that associated with tuberculosis. In the current study we aimed to explore the genetic association of polymorphisms of IFNG and IFNGR1 with the risk of pulmonary tuberculosis (PTB) in the Chinese Tibetan population. We selected 467 PTB patients and 503 healthy controls to genotype 9 single nucleotide polymorphisms (SNPs). The unconditional logistic regression analysis was applied for assessing the associations, and the risk of PTB were evaluated by calculating the odds ratio (OR) and 95% confidence interval (CI). The results showed that mutants of rs9376268, rs1327475 and rs1327474 in IFNGR1 played a protective role in the PTB risk under genotype, dominant and additive model (P<0.05). On the contrary, minor allele "A" of rs2069705 in IFNG significantly increased the risk of PTB under genotype, dominant and additive model (P<0.05). However, after Bonferroni's multiple adjustment was applied to our data, which level of significant was set at P<0.0011 (0.05/45). Only variant of rs9376268 was significantly associated decrease the PTB susceptibility under additive model (OR=0.73, 95%CI=0.61-0.88, P<0.001). Furthermore, in the haplotype analysis, we found that the haplotypes "C-G-G-A-C", "C-G-A-G-T" and "T-A-G-G-T" of rs9376267-rs9376268-rs1327475-rs7749390-rs1327474 block were extremely decreased the PTB risk (P<0.01), however, the haplotypes "C-G-G-A-T", "T-G-G-G-T" and "C-G-G-G-T" of the block were extremely increased the PTB risk (P<0.01). These results suggested that variants of IFNGR1 may have a close relation with the PTB risk in Chinese Tibetan population.

Association between TAP2 and SEC14L2 polymorphisms and pulmonary tuberculosis risk in the Tibetan Chinese population.

AIM: Pulmonary tuberculosis (PTB) is an infectious disease with a high incidence worldwide. Previous genome-wide association studies have identified multiple susceptibility loci for pulmonary tuberculosis (PTB); however, validation of these findings is still needed. METHODS: For this study, we recruited 300 subjects with PTB and 300 healthy subjects from a Tibetan population living in near or in Xi'an, China. Association analyses of single-nucleotide polymorphisms (SNPs) in TAP2 and SEC14L2 were performed with SPSS Statistics (version 17.0), SNPStats, Haploview (version 4.2), and SHEsis software. RESULTS: We found a correction between one SNP (rs1061660) and PTB based on Chi-square or Fisher's exact tests. In the allelic model analysis, the SNPs rs1061660 in SEC14L2 gene increased PTB 1.32-fold risk (OR = 1.32, CI = 1.05-1.66, P = 0.017). In the genetic model analysis, the rs3819721 in TAP2 gene was associated with increased 1.65-fold risk in the co-dominant model and 1.67-fold risk in the over-dominant model, respectively. For the rs1061660 in SEC14L2 gene, we found it was associated with a 1.49-fold increase the risk of PTB in the dominant model and a 1.37-fold increase the risk of PTB in the log-additive model, respectively. CONCLUSION: We found that two SNPs are associated with increased PTB risk in the Chinese Tibetan population.

Association of ADAM33 gene with susceptibility to COPD in Tibetan population of China.

Chronic obstructive pulmonary disease (COPD) is a common, complex disorder associated with substantial morbidity and mortality, influenced by both environmental factor and genetic factor. ADAM33 gene was found to be associated with asthma, declined lung function and COPD. The purpose of the study was to test whether SNPs in ADAM33 were associated with COPD in Tibetan population of China. Polymerase chain reaction-restriction fragment length polymorphism was carried out to genotype the eight SNPs (V4, T2, T1, S2, S1, Q-1 and F + 1) of ADAM33 on 240 COPD patients and 221 healthy individuals. Four SNPs (V4, T2, T1 and S1) and four haplotypes (H2 CGAAGAGC, H5 GAGAGAGC, H9 GAAAGAGC and H6 CGGGGAGC of ADAM33 gene were associated with COPD significantly (defined as P < 0.05). The results indicate that there is an association between ADAM33 polymorphisms and COPD in Tibetan population of China.