Association of leptin and leptin receptor genes variants and pulmonary tuberculosis susceptibility, clinical manifestations in a Chinese population.

BACKGROUND: The aim of our study was to investigate the association of leptin (LEP) gene (rs11761556, rs12706832, rs2167270), leptin receptor (LEPR) gene (rs1137100, rs1137101, rs1805096) variants and pulmonary tuberculosis (PTB) susceptibility, as well as their several clinical manifestations, in a Chinese population. METHODS: This study included a cohort of 489 PTB patients and 489 healthy controls, and six SNPs were genotyped by improved multiple ligase detection reaction (iMLDR). RESULTS: We found that there were no significant differences regarding the allele and genotype frequencies of LEP rs11761556, rs12706832, rs2167270, LEPR rs1137100, rs1137101, rs1805096 between PTB patients and healthy controls (all P > 0.05), as well as the results of the dominant model and recessive model (all P > 0.05). In the LEP gene, the rs11761556 AA genotype frequency was significantly associated with the development of fever and pulmonary infection in PTB patients (P = 0.035, P = 0.049). In addition, the relation between main haplotypes and PTB patients was also analyzed, but only haplotype CAG in LEP was significantly associated with PTB susceptibility (P = 0.012). CONCLUSIONS: LEP and LEPR heritable variation were not contribute to the pathogenesis of PTB in Chinese. While rs11761556 variant might associate with several clinical features of PTB.

The mRNA expression of visfatin and lipocalin-2 in peripheral blood mononuclear cells from patients with pulmonary tuberculosis.

BACKGROUND: In this study, we aimed to assess mRNA expressions of visfatin and lipocalin-2 in peripheral blood mononuclear cells (PBMCs) from patients with pulmonary tuberculosis (PTB). METHODS: Overall, 79 PTB patients and 71 healthy controls were enrolled. In PBMCs, mRNA expressions of visfatin and lipocalin-2 were detected using real-time quantitative polymerase chain reaction (qRT-PCR), and the diagnostic value of these adipokine mRNAs in PTB patients was calculated through receiver operating characteristic (ROC) analysis. RESULTS: In PBMCs from PTB patients, the visfatin mRNA level was significantly higher than in healthy controls (P < .001), with no significant association between the lipocalin-2 mRNA level and PTB patients (P = .933). In PTB patients, lipocalin-2 mRNA expression positively correlated with the erythrocyte sedimentation rate (ESR) (P = .010). However, the visfatin mRNA level was not associated with any major clinical and laboratory parameter in PTB patients. The ROC curve demonstrated that visfatin could help distinguish PTB patients from healthy controls, with an optimal cutoff value of 0.645 and a corresponding sensitivity of 79.7%. CONCLUSIONS: The altered visfatin mRNA expression indicated that this adipokine might play a role in PTB and could be an auxiliary biomarker for PTB diagnosis.

Association of adiponectin and adiponectin receptor gene polymorphisms with rheumatoid arthritis in a Chinese population.

PURPOSE: To explore the association of adiponectin (AD) and adiponectin receptor (ADR) gene single-nucleotide polymorphisms (SNPs) with genetic susceptibility to rheumatoid arthritis (RA) in a Chinese population. STUDY DESIGN: Five AD SNPs (rs266729, rs2241766, rs1063537, rs2082940 and rs1063539) and two ADR SNPs (rs7539542 and rs12342) were genotyped in a cohort of 617 patients with RA and 639 healthy controls. Seven SNPs were genotyped using TaqMan genotyping assays on the Fluidigm 192.24 system. The concentration of AD in plasma was examined by ELISA. RESULTS: Patients with RA showed a considerably lower plasma level of AD than healthy controls (p=0.002). No significant differences were observed for the distribution of allele and genotype frequencies of rs266729, rs2241766, rs2082940, rs1063539, rs7539542 and rs12342 SNPs between patients with RA and controls. The genotype effects of recessive and dominant models were also analysed, but no marked evidence for association was found. However, further analysis in female patients with RA showed that the frequency of the AD gene rs1063539 GG genotype was nominally significantly higher in patients who were anti-cyclic citrullinated peptide (anti-CCP) antibody-positive (p=0.040). No significant differences in serum AD level were observed in patients with RA with different genotypes. CONCLUSIONS: rs266729, rs2241766, rs2082940 and rs1063539 in the AD gene and rs7539542 and rs12342 in the ADR gene are possibly not associated with genetic susceptibility to RA, but the A D gene rs1063539 locus was possibly associated with anti-CCP in RA female patients.

Altered mRNA expression levels of vaspin and adiponectin in peripheral blood mononuclear cells of systemic lupus erythematosus patients.

OBJECTIVES: Increasing studies have indicated the association between adipokines and multiple autoimmune diseases. This study aimed to evaluate the mRNA expression levels of vaspin, adiponectin and adrenomedullin in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE), as well as their clinical associations. METHODS: A total of 46 SLE patients and 51 normal controls were recruited. The three adipokines expression levels in PBMCs from SLE patients were measured by qRT-PCR, and their associations with major clinical and laboratory parameters of SLE patients were also analysed. RESULTS: Compared with normal controls, vaspin expression level in PBMCs was significantly decreased (p<0.001), whereas adiponectin expression level was significantly higher in SLE patients (p<0.001). There was no significant difference in adrenomedullin expression level between SLE patients and normal controls. Vaspin and adrenomedullin expression levels in more active SLE were significantly lower than those in less active SLE (p=0.012, p=0.046, respectively). No significant difference in these adipokine expression levels was observed between SLE patients with and without lupus nephritis (LN). There was also no significant association between mRNA levels of these adipokines and major clinical and laboratory parameters. CONCLUSIONS: Altered vaspin, adiponectin expression levels, and the associations between vaspin, adrenomedullin levels and disease activity in SLE patients suggested that these adipokines might play a role in SLE.

A Meta-Analysis of Cardiovascular Events in Systemic Lupus Erythematosus.

Objective: To identify accurate occurrence and risk of cardiovascular (CV) events (stroke and myocardial infarction [MI]) in patients with systemic lupus erythematosus (SLE). Methods: Systemic literature search in PubMed and additional manual search were performed to obtain interested studies until March 31, 2018. The pooled incidences and risk of stroke and MI were calculated. Results: A total of 24 studies were included in this meta-analysis. For MI, a total of 1,516 SLE patients were reported to had MI (n = 96,154) over a mean follow-up of 9.98 years: incidence 2.0% (95% CI: 1.7-2.4%), i.e. 0.20/100 pyrs; in the five studies, 360 SLE patients (n = 18,943) and 817 controls had MI (n = 111,525), revealing that the risk of MI in SLE population was 3.04 times higher than in the general population (RR = 3.04, 95% CI: 1.81-5.11). For stroke, the incidence of 17 studies during the 10.09 follow-up period using random model was 4.4% (95% CI: 3.6-5.1%), i.e. 0.44/100 pyrs; in the 7 studies, 694 SLE patients (n = 22,594) and 4,034 controls had stroke (n = 255,023), indicating that the risk of MI in SLE population was 1.95 times higher than that in the general population (RR = 1.95, 95% CI: 1.52-2.53). Conclusion: Based on the findings from previous reports, our meta-analysis showed that patients with SLE have been at higher risk of CV events.

The expression levels of long noncoding RNAs lnc0640 and lnc5150 and its gene single-nucleotide polymorphisms in rheumatoid arthritis patients.

OBJECTIVES: The aim of our study was to evaluate two lncRNAs (lnc0640 and lnc5150) expressions and gene single-nucleotide polymorphisms (SNPs) in rheumatoid arthritis (RA) patients. METHODS: The expressions of lncRNAs in peripheral blood mononuclear cells (PBMCs) were examined by quantitative real-time reverse transcription polymerase chain reaction from 65 RA patients and 54 controls. Simultaneously, three SNPs (rs13039216, rs6085189, and rs6085190) of lnc0640, three SNPs (rs1590666, rs141561256, and rs144047453) of lnc5150 were genotyped using TaqMan SNP-genotyping assays in 627 RA patients and 590 controls. RESULTS: The lnc0640 level in PBMCs from RA patients was significantly increased (P = 0.001), whereas the lnc5150 level was significantly reduced (P < 0.001) compared to controls. There were significant associations of lnc0640 and lnc5150 levels with C-reactive protein in RA patients (P = 0.011 and P = 0.014, respectively), while lnc5150 level was associated with erythrocyte sedimentation rate (P = 0.022). TT genotype of rs13039216 in lnc0640 gene was statistically associated with a reduced risk of RA (TT vs CC; P = 0.046), and a decreased risk of rs13039216 variant was observed under the recessive model (P = 0.038). In addition, the G allele of rs141561256 polymorphism in lnc5150 gene was significantly associated with rheumatoid factor in RA patients (P = 0.034). There were no associations between lnc0640 and lnc5150 levels and their respective genotype in RA patients. CONCLUSIONS: The expressions of lnc0640 and lnc5150 were alternated in the RA patients, suggesting that these lncRNAs may involve in the development of RA.

Association of single nucleotide polymorphisms in resistin gene with rheumatoid arthritis in a Chinese population.

BACKGROUND: Recent evidences have revealed that resistin is associated with the development of rheumatoid arthritis (RA). The aim of this study was to analyze the association of resistin gene single nucleotide polymorphisms (SNPs) with RA susceptibility. METHODS: In this study, we finally analyzed three resistin SNPs (rs1862513, rs3745368, and rs3745367) in 278 RA patients and 276 normal controls recruited from Chinese population using TaqMan SNP genotyping assays. RESULTS: There were no significant differences for the distribution of allele and genotype frequencies of these three SNPs between RA patients and normal controls (all P > .05). The genotype effects of dominant, recessive models were also analyzed, and no significant association was detected (all P > .05). Haplotype analysis suggested that the frequency of haplotype GAA was notably lower in RA patients in comparison with normal controls (OR = 0.317, 95% CI: 0.125-0.807, P = .011). CONCLUSION: In a ward, our results indicated that resistin gene polymorphisms might affect the genetic predisposition of RA in Chinese population.

Association of interleukin-10 gene single nucleotide polymorphisms with rheumatoid arthritis in a Chinese population.

PURPOSE OF THE STUDY: Increasing numbers of studies show that interleukin (IL)-10 plays a key role in the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) and acts as an immunomodulatory cytokine. The purpose of the present study was to analyse the relationship between gene single nucleotide polymorphisms (SNPs) in the IL-10 gene and RA susceptibility. STUDY DESIGN: We genotyped three SNPs (rs1800890, rs3024495, rs3024505) of the IL-10 gene in a Chinese population of 354 RA patients and 367 controls. Genotyping was conducted using TaqMan SNP genotyping assays. Plasma IL-10 levels were measured by ELISA. RESULTS: The A allele of the rs1800890 variant was significantly related to decreased risk for RA compared with the T allele (A vs T: OR 0.580, 95% CI 0.345 to 0.975, P=0.038). No significant association between the genotype distribution of these SNPs and RA susceptibility was detected. The genotype effect of the dominant model was also evaluated, but no statistical difference was found. Further analysis in RA patients demonstrated that none of these SNPs were associated with rheumatoid factor (RF) or anti-citrullinated protein antibody (anti-CCP). In addition, no significant differences in plasma IL-10 levels were observed among RA patients with different genotypes. CONCLUSIONS: The IL-10 rs1800890 variant might contribute to RA susceptibility in the Chinese population. Replication studies in different ethnic groups are required to further examine the critical role of IL-10 gene variation in the pathogenesis of RA.

Association of leptin and leptin receptor gene polymorphisms with systemic lupus erythematosus in a Chinese population.

To explore the association of LEP and leptin receptor (LEPR) gene single-nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. Four LEP SNPs (rs11761556, rs12706832, rs2071045 and rs2167270) and nine LEPR SNPs (rs10749754, rs1137100, rs1137101, rs13306519, rs8179183, rs1805096, rs3790434, rs3806318 and rs7518632) were genotyped in a cohort of 633 patients with SLE and 559 healthy controls. Genotyping of SNPs was performed with improved multiple ligase detection reaction (iMLDR). No significant differences were detected for the distribution of allele and genotype frequencies of all 13 SNPs between patients with SLE and controls. The genotype effects of recessive, dominant and additive models were also analysed, but no significant evidence for association was detected. However, further analysis in patients with SLE showed that the TT genotype and T allele frequencies of the LEP rs2071045 polymorphism were nominally significantly higher in patients with pericarditis (P = 0.012, P = 0.011, respectively). In LEPR, the GA/AA genotype and A allele frequencies of the rs1137100 polymorphism were both nominally associated with photosensitivity in patients with SLE (P = 0.043, P = 0.018, respectively). Moreover, the genotype and allele distribution of rs3806318 were also nominally associated with photosensitivity in patients with SLE (P = 0.013, P = 0.008, respectively). No significant differences in serum leptin levels were observed in patients with SLE with different genotypes. In summary, LEP and LEPR SNPs are not associated with genetic susceptibility to SLE, but may contribute to some specific clinical phenotype of this disease; further studies are necessary to elucidate the exact role of LEP and LEPR genes in the pathogenesis of SLE.

Association of HLA-DQB1 polymorphisms with rheumatoid arthritis: a meta-analysis.

AIM: Studies investigating the association between HLA-DQB1 alleles and rheumatoid arthritis (RA) have reported conflicting results. The purpose of this study was to evaluate whether DQB1 alleles confer susceptibility to RA. DESIGN: A comprehensive literature search up to May 2016 was conducted to identify case-control studies on the association of HLA-DQB1 alleles with RA. Pooled ORs with 95% CIs were used to assess the strength of association. SETTING: The literature indicates that HLA-DQB1 is associated with susceptibility to RA. MAIN OUTCOME MEASURES: Frequencies of HLA-DQB1 alleles and phenotype in RA patients and healthy controls. RESULTS: Fifteen studies with 1250 cases and 1621 controls were included in this meta-analysis. DQB1 alleles were associated with RA susceptibility. The frequencies of DQB1*06 were lower in RA (p-value for comparability=0.007, OR 0.726,95% CI 0.576 to 0.916; p=0.004, OR 0.611,95% CI 0.438 to 0.852). The frequencies of DQB1*02 were lower in RA (p=0.044, OR 0.731,95% CI 0.597 to 0.895). A higher frequency of DQB1*04 was observed in RA (p=0.023, OR 1.604,95% CI 1.067 to 2.410). CONCLUSIONS: This meta-analysis demonstrates that DQB1*02 and DQB1*06 may be negatively associated with RA. Conversely, DQB1*04 may confer susceptibility to RA.

Plasma levels of adipokines in systemic lupus erythematosus patients.

OBJECTIVE: To evaluate the plasma levels of six adipokines, including chemerin, omentin-1, lipocalin-2, cathepsin-S, cathepsin-L and adipsin, in patients with SLE. METHODS: Ninety SLE patients and ninety control subjects were recruited, plasma adipokines levels were measured by enzyme-linked immunosorbent assay, and their associations with major clinical and laboratory indexes were analyzed. RESULTS: There were no significant differences in plasma chemerin, omentin-1, lipocalin-2, cathepsin-S, cathepsin-L and adipsin levels between SLE patients and controls. Further subgroup analyses by major clinical and laboratory indexes showed that plasma omentin-1 level was significantly lower in SLE patients without nephritis when compared with those patients with nephritis (P=0.002). Plasma chemerin, cathepsin-S levels in SLE patients without nervous system disorder were significantly lower in comparison with SLE patients with nervous system disorder (P=0.035, P=0.029). No significant associations of other adipokines with any major clinical and laboratory indexes were observed. CONCLUSIONS: Plasma levels of chemerin, omentin-1, lipocalin-2, cathepsin-S, cathepsin-L and adipsin in SLE patients were not markedly different from the normal controls. The presence of nephritis was connected with higher plasma omentin-1 levels in SLE patients, and the presence of nervous system disorder was associated with higher plasma chemerin, cathepsin-S levels in SLE patients. However, functional studies are awaited to further explore the potential roles of these cytokines in SLE.

Relationship between the IL12B (rs3212227) gene polymorphism and susceptibility to multiple autoimmune diseases: A meta-analysis.

OBJECTIVES: The purpose of this study was to evaluate whether a single-nucleotide polymorphism (SNP) IL12B 3(')UTR +1188A/C (rs3212227) confers susceptibility to several autoimmune diseases. METHODS: A systematic literature search was conducted to identify relevant studies. Pooled odds ratio (OR) with 95% confidence interval (CI) was used to estimate the strength of association. RESULTS: Twenty-five studies were included in the meta-analysis, which contained 9794 cases and 11,330 controls. Our result indicated that IL12B +1188A/C (rs3212227) polymorphism was associated with type-1 diabetes (T1D) in the dominant model (p = 0.008), and an increased risk was found in East Asians in the dominant model (p < 0.001). East Asians rheumatoid arthritis (RA) patients seemed to be at risk of allelic model (p = 0.011). As to Behcet's disease (BD), there was a risk in dominant model (p = 0.020) and positive associations of dominant model, allelic model in East Asians (p = 0.009; p < 0.001, respectively). But we failed to find any association between IL12B +1188A/C (rs3212227) polymorphism with Graves' disease (GD) and ankylosing spondylitis (AS). CONCLUSIONS: The present study suggests that the IL12B +1188A/C (rs3212227) polymorphism might be associated with genetic susceptibility to autoimmune diseases, such as T1D, RA, BD, but not GD and AS.

Short-term exposure to gaseous pollutants is neglected factors for knee osteoarthritis: evidence from a humid subtropical region of China.

Few studies were performed on the impact of exposure to gaseous pollutants on the risk of knee osteoarthritis (KOA). We conducted this study to analyze the association between short-term exposure to gaseous pollutants and the risk of hospitalizations for KOA. A total of 2952 KOA hospitalizations derived from two hospitals in Hefei, and the relationship between gaseous pollutants and KOA hospitalizations was analyzed by a distributed lag non-linear model combined with a generalized linear model. We found that the decreased risk of hospitalizations for KOA were both related to exposure to NO2 (RR = 0.993, lag19 day) and O3 (RR = 0.984, lag0 day), while exposure to CO could increase the risk of hospitalizations for KOA (RR = 1.076, lag2 day). Stratified analyses suggested that the KOA patients < 65 years were more susceptible to O3 exposure, and the female, male, patients ≥ 65 years, and patients < 65 years were both more sensitive to CO exposure. Our findings demonstrated that exposure to NO2, O3 resulted in a decreased risk for KOA hospitalizations, and CO exposure might increase the risk of KOA hospitalizations.

The Methylation in B7-H4 and BTLA Genes are Associated with the Risk of Pulmonary Tuberculosis.

Background: The important roles of B7 homologous body 4 (B7-H4), B and T lymphocyte attenuator (BTLA) in patients with pulmonary tuberculosis (PTB) have been reported. This study aims to evaluate the association among B7-H4 and BTLA genes polymorphism, methylation and PTB susceptibility. Methodology: Here, we assessed the possible relationship of 10 single nucleotide polymorphisms (SNPs) in B7-H4, BTLA genes with PTB susceptibility in a Chinese population (496 PTB patients and 502 controls) by SNPscan technique. Then, the B7-H4, BTLA genes methylation levels among 98 PTB patients and 97 controls were detected using MethylTarget technique. Results: This study found no significant differences in allele and genotype frequencies of B7-H4 gene rs10754339, rs10801935, rs10923223, rs1937956, rs3738414, BTLA gene rs1982809, rs2971205, rs75368388, rs9288953 variants between PTB patients and controls. Haplotype analysis suggested that the lower frequencies of B7-H4 AATTG haplotype, BTLA GATT haplotype and the higher frequency of BTLA AGTC haplotype were found in PTB patients when compared with controls. We also found that the frequency of BTLA gene rs9288953 C allele was significantly increased in PTB patients with drug resistance. Moreover, the methylation levels of B7-H4 and BTLA genes in PTB patients were greater than that in controls, and rs10754339 variant in B7-H4 gene could affect its methylation level in PTB patients. Conclusion: B7-H4, BTLA genes polymorphism might not affect PTB susceptibility, while the abnormal methylation levels of B7-H4, BTLA genes were associated with the genetic background of PTB.

Association of lncRNA THRIL, HOTAIR genes variations and expression levels with pulmonary tuberculosis.

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.

Impact of m6A demethylase (ALKBH5, FTO) genetic polymorphism and expression levels on the development of pulmonary tuberculosis.

Objective: The 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. Methods: Eight 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. Results: The 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. Conclusion: FTO 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.

Association Between Genetic Polymorphisms of lncRNA NEAT1 and Pulmonary Tuberculosis Risk, Clinical Manifestations in a Chinese Population.

Background: Recent studies have shown that abnormal expression of lncRNA NEAT1 is associated with the progression of pulmonary tuberculosis (PTB). The aim of our study was to analyze the relationship between single nucleotide polymorphisms (SNPs) of NEAT1 gene and susceptibility to PTB. Methods: Four SNPs (rs2239895, rs3741384, rs3825071, rs512715) in NEAT1 gene were genotyped in 479 patients with PTB and 476 controls by improved multiple ligase detection reaction (iMLDR) in a Chinese population. Results: We found no significant differences in allele and genotype frequencies of NEAT1 gene rs2239895, rs3741384, rs3825071, rs512715 between PTB patients and controls (all P > 0.05). There was no statistically significant association between genotype frequency distribution of dominant model, as well as recessive model, and genetic susceptibility to PTB patients (all P > 0.05). The TT genotype, T allele frequencies of rs3825071 were significantly increased in sputum smear-positive PTB patients when compared to sputum smear-negative PTB patients (P = 0.010, P = 0.003, respectively). Haplotype analysis shown that NEAT1 haplotype frequency was not associated with PTB susceptibility. Conclusion: NEAT1 gene polymorphisms were not associated with the risk of PTB in Chinese population, and rs3825071 polymorphism might be related to sputum smear-positive in PTB patients.

Exploring the association between Th17 pathway gene polymorphisms and pulmonary tuberculosis.

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.

Clinical relevance of vitamin B12 level and vitamin B12 metabolic gene variation in pulmonary tuberculosis.

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.

Investigation on Probable Association Between IL-13, IL-13RA1, and IL-13RA2 Genes Polymorphism and Pulmonary Tuberculosis.

Objective: Our study aimed to explore the association of IL-13, IL-13RA1, and IL-13RA2 genes polymorphisms with PTB susceptibility and its clinical features. Methods: Nine SNPs were genotyped by improved multiple ligase detection reaction (iMLDR) in 476 PTB patients and 473 controls. The association between these SNPs and PTB risk was analyzed using SPSS software and haplotype analysis was assessed using SHEsis software. Results: The IL-13RA1 rs2495636 GA genotype frequency in PTB patients was significantly decreased, and IL-13RA2 rs5946039 A allele was related to the lower risk of PTB. In IL-13 gene, rs20541 variant was found to be associated with PTB risk under recessive mode. Moreover, IL-13RA1 rs141573089 C allele was significantly lower in PTB presenting with fever, drug resistance, and CC genotype was decreased in PTB presenting with leukopenia. IL-13RA1 rs2495636 polymorphism was associated with drug resistance, pulmonary infection, and IL-13RA2 rs3795175, rs638376 polymorphisms were related to drug resistance in PTB patients. Conclusion: IL-13 rs20541, IL-13RA1 rs2495636, IL-13RA2 rs5946039 polymorphisms might be contributed to the genetic background of PTB in Chinese population.