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Abstract Background Long non-coding RNA (lncRNA) has been implicated in the pathogenesis of pulmonary tuberculosis (PTB). This study aims to investigate the involvement of lncRNA THRIL and HOTAIR gene single nucleotide polymorphisms (SNPs) and their expression levels in PTB susceptibility. Methods A total of 456 PTB patients and 464 healthy controls participated in our study. we genotyped six SNPs of THRIL and HOTAIR genes using an improved multiple ligase detection reaction (iMLDR). Additionally, real-time reverse-transcriptase polymerase chain reaction was employed to detect the expression levels of THRIL and HOTAIR in peripheral blood mononuclear cells (PBMC) from 78 PTB patients and 84 healthy controls. Results No significant differences in allele and genotype frequencies were observed for THRIL rs1055472, rs11058000, and HOTAIR rs12427129, rs1899663, rs4759314, and rs7958904 polymorphisms between PTB patients and healthy controls (all P > 0.05). Moreover, genotype frequencies of all SNPs did not show any association with PTB susceptibility in the dominant–recessive model. However, the frequencies of rs7958904 CC genotype and C allele in the HOTAIR gene were significantly correlated with leukopenia in PTB patients. Furthermore, the expression levels of the HOTAIR gene were significantly elevated in PTB patients compared to controls. Conclusions Our study indicates that THRIL and HOTAIR gene SNPs might not contribute to PTB susceptibility, while the level of HOTAIR was increased in PTB patients.

ObjectiveThe m6A methylation was involved in the pathogenesis of pulmonary tuberculosis (PTB), and our study aimed to reveal the potential association of m6A demethylase (ALKBH5, FTO) genes variation, expression levels and PTB.MethodsEight SNPs (ALKBH5 gene rs8400, rs9913266, rs12936694, rs4925144 and FTO gene rs6499640, rs8047395, rs1121980, rs9939609) were selected for genotyping by SNPscan technique in 449 PTB patients and 463 healthy controls.ResultsThe mRNA expression levels of ALKBH5, FTO were detected by qRT-PCR. There were no significant differences in genotype, allele distributions of all SNPs between PTB patients and healthy controls. Haplotype analysis demonstrated that the frequency of FTO gene GAAA haplotype was significantly reduced in PTB patients when compared to controls. ALKBH5 rs8400 AA genotype, A allele frequencies were associated with the decreased risk of sputum smear-positive, while AA genotype frequency was related to the increased risk of hypoproteinemia in PTB patients. In addition, rs9913266 variant was linked to the occurrence of drug-induced liver injury, sputum smear-positive, and rs4925144 variant was associated with leukopenia among PTB patients. In FTO gene, rs8047395 GG genotype and G allele frequencies were significantly higher in the PTB patients with drug resistance than that in the PTB patients without drug resistance. The ALKBH5, FTO expression levels were significantly decreased in PTB patients in comparison to controls. Moreover, ALKBH5 level was increased in PTB patients with drug resistance, and FTO level was decreased in PTB patients with sputum smear-positive.ConclusionFTO gene polymorphisms might be associated with PTB susceptibility, and ALKBH5, FTO levels were decreased in PTB patients, suggesting that these m6A demethylase played important roles in PTB.

ObjectiveThe aim of the current study was to investigate the contributing role of gene variation and transcription levels among the m6A methyltransferases METTL3, METTL14, and WTAP in pulmonary tuberculosis (PTB).MethodsA case-control study including 461 PTB patients and 467 normal controls was designed for genotyping. Three SNPs in METTL3 (rs1061027, rs1139130, rs1061026), three SNPs in METTL14 (rs62328061, rs4834698, rs1064034), and two SNPs in WTAP (rs1853259, rs11752345) were genotyped via the SNPscan™ technique. METTL3, METTL14, and WTAP transcription levels were determined in 78 PTB patients and 86 controls via quantitative real-time reverse-transcription PCR.ResultsFrequencies of the METTL14 rs62328061 GG genotype, WTAP rs11752345 CT genotype, and T allele were significantly increased in PTB patients compared to controls. An increased risk of rs62328061 was detected in a recessive model, and a decreased risk of rs11752345 was detected in a dominant model in the PTB group. METTL3 gene variation was not associated with PTB risk. The METTL3 rs1139130 GG genotype was significantly increased with drug resistance, and the G allele was significantly decreased with drug-induced liver injury in PTB patients. A reduced frequency of the METTL14 rs62328061 G allele was associated with leukopenia, a reduced frequency of the WTAP rs11752345 T allele was associated with sputum smear positivity, and a higher frequency of the METTL14 rs4834698 TC genotype was evident in PTB patients with hypoproteinemia. Compared to controls, METTL3, METTL14, and WTAP transcription levels in PTB patients were significantly decreased, and the level of WTAP was increased in PTB patients with drug resistance. METTL3 level was negatively associated with erythrocyte sedimentation rate and aspartate aminotransferase, and METTL14 level was negatively correlated with alanine aminotransferase and aspartate aminotransferase.ConclusionMETTL14 rs62328061 and WTAP rs11752345 variants were associated with the genetic background of PTB, and METTL3, METTL14, and WTAP levels were abnormally decreased, suggesting that these m6A methyltransferases may play important roles in PTB.

Th17 cells play a key role in immunity against Mycobacterium tuberculosis (MTB), and this study aimed to explore the association of Th17 pathway gene polymorphisms with pulmonary tuberculosis (PTB) susceptibility in a Chinese population. A total of 10 single nucleotide polymorphisms in Th17 pathway genes (IL-17A gene rs2275913, rs3748067, rs8193036, rs3819024, IL-17F gene rs7741835, rs763780, IL-21 gene rs907715, rs2055979, IL-23R gene rs11805303, and rs7518660) were genotyped in 456 PTB patients and 466 controls using SNPscan technique. The IL-23R rs11805303 CC genotype, C allele frequencies were significantly lower in PTB patients than in controls, and the rs11805303 variant was significantly associated with the reduced risk of PTB in a recessive model. There were no significant associations between IL-17A, IL-17F, and IL-21 gene variations and PTB risk. In IL-17A gene, rs2275913, rs3748067, and rs3819024 variants were associated with drug resistance in PTB patients. In IL-17F gene, rs7741835 variant affected drug resistance, and rs763780 variant was associated with hypoproteinemia in PTB patients. In addition, the lower frequencies of the TT genotype, T allele of rs2055979 were found in PTB patients with drug-induced liver injury. Haplotype analysis showed that IL-23R CG haplotype frequency was significantly lower in PTB patients than in controls, while the TG haplotype frequency was higher. In conclusion, IL-23R rs11805303 polymorphism may contribute to the genetic underpinnings of PTB in the Chinese population, and the IL-17A, IL-17F, and IL-21 genetic variations are associated with several clinical manifestations of PTB patients.

The aim of this study was to assess the association of vitamin B12 level and single nucleotide polymorphisms (SNPs) in vitamin B12 metabolic genes with pulmonary tuberculosis (PTB) in Chinese Han population. The plasma vitamin B12 expression level was detected using ELISA. Ten SNPs in six key genes (TCN1, TCN2, CUBN, MMACHC, FUT6, and MUT) of vitamin B12 metabolic pathway were included for genotyping by the SNPscan technique among 454 PTB patients and 467 controls. Our results found that vitamin B12 level was significantly reduced in PTB patients when compared with controls. There was no significant association between TCN1 rs526934, TCN2 rs1801198, CUBN rs7906242, rs10904861, rs1801222, MMACHC rs10789465, FUT6 rs3760776, rs3760775, MUT rs9473555, rs9381784 variants, and PTB susceptibility. TCN2 rs1801198 CC genotype, C allele was significantly associated with hypoproteinemia in PTB patients. In CUBN, rs7906242 GG genotype, G allele, rs10904861 TT genotype, and T allele were significantly related to the decreased frequency of sputum smear-positive, and rs10904861 variant affected the occurrence of drug resistance in PTB patients. In addition, the increased frequency of CUBN rs1801222 AA genotype was significantly associated with leukopenia. The decreased frequency of MUT rs9473555 CC genotype was found in the PTB patients with hypoproteinemia. However, vitamin B12 expression was not associated with the genotype distribution of above SNPs. In conclusion, vitamin B12 level was significantly decreased in PTB patients and genetic variants in vitamin B12 metabolic genes were not contributed to PTB susceptibility. Several SNPs in TCN2, CUBN, and MUT gene might associate with multiple clinical manifestations in PTB.

N6-Methyladenosine (m6A) is associated with many biological processes and the development of multiple diseases. The aim of this study was to analyze the association of m6A readers' genes variation, as well as their expression levels, with pulmonary tuberculosis (PTB). A total of 11 single-nucleotide polymorphisms (SNPs) in m6A readers' genes (i.e., YTHDF1 rs6122103, rs6011668, YTHDF2 rs602345, rs3738067, YTHDF3 rs7464, rs12549833, YTHDC1 rs3813832, rs17592288, rs2293596, and YTHDC2 rs6594732, and rs2416282) were genotyped by SNPscan™ technique in 457 patients with PTB and 466 normal controls. The m6A readers' genes expression levels in peripheral blood mononuclear cells (PBMCs) from 78 patients with PTB and 86 normal controls were detected by quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). There was no significant association between all SNPs in YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2 genes and PTB susceptibility. The increased frequencies of YTHDF2 rs3738067 GG genotype and YTHDC1 rs3813832 CC genotype, C allele, were, respectively, found in PTB patients with hypoproteinemia and fever. YTHDC2 rs6594732 variant was significantly associated with drug-induced liver damage and sputum smear-positive, and the rs2416282 variant was significantly associated with fever in patients with PTB. Compared with controls, the YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2 mRNA levels were significantly decreased in PTB. Moreover, YTHDF1 level was negatively associated with erythrocyte sedimentation rate (ESR), and YTHDF3 and YTHDC1 levels were negatively related to alanine aminotransferase (ALT) in patients with PTB. Our results demonstrated that YTHDF1, YTHDF2, YTHDF3, YTHDC1, and YTHDC2 genes SNPs did not contribute to PTB susceptibility, while their decreased levels in patients with PTB suggested that these m6A readers might play significant roles in PTB.