Tuberculosis Susceptibility Research Articles

Association of IL-6 rs1800796 Gene Polymorphism on Susceptibility to Pulmonary Tuberculosis

Introduction: Tuberculosis (TB) is still the leading cause of mortality and morbidity around the globe, particularly in underdeveloped nations. Indonesia is listed as the country with the second-largest TB burden in the world according to Global TB Report 2020. Only 10% of those infected with Mycobacterium tuberculosis (MTB) develop active TB and the great majority continues to stay latently infected, indicating that the host response to MTB may be genetically controlled at each stage. A growing number of studies have shown that numerous host genetic variables have a role in TB susceptibility. IL-6 is a pro-inflammatory cytokine produced by monocytes, endothelial cells, and fibroblasts that stimulates B and T lymphocytes while also controlling the immune response to TB. This study investigated the association of IL-6 rs1800796 gene polymorphism on susceptibility to pulmonary TB in drug-sensitive (DS) or drug-resistant (DR) patients. Methods: The case-control study involved 71 cases and 34 controls. Blood samples were taken from all study participants at Dr. Saiful Anwar General Hospital, Malang between August 2020 and February 2021. To determine SNPs, blood samples were used in a genotyping investigation using the PCR-Multiplex technique. Results: The genotype association of IL-6 rs1800796 (G/G, G/C, C/C) and allele frequency for patients and controls of IL-6 rs1800796 with susceptibility to pulmonary TB were insignificant (p > 0.05). Conclusion: This study found no evidence of association of IL-6 rs1800796 gene polymorphism with susceptibility to pulmonary TB.

CHARACTERIZING TUBERCULOSIS PROGRESSION IN WILD MEERKATS (SURICATA SURICATTA) FROM FECAL SAMPLES AND CLINICAL SIGNS.

Tuberculosis (TB) is an increasing threat to wildlife, yet tracking its spread is challenging because infections often appear to be asymptomatic, and diagnostic tools such as blood tests can be invasive and resource intensive. Our understanding of TB biology in wildlife is therefore limited to a small number of well-studied species. Testing of fecal samples using PCR is a noninvasive method that has been used to detect Mycobacterium bovis shedding amongst badgers, yet its utility more broadly for TB monitoring in wildlife is unclear. We combined observation data of clinical signs with PCR testing of 388 fecal samples to characterize longitudinal dynamics of TB progression in 66 wild meerkats (Suricata suricatta) socially exposed to Mycobacterium suricattae between 2000 and 2018. Our specific objectives were 1) to test whether meerkat fecal samples can be used to monitor TB; 2) to characterize TB progression between three infection states (PCR-negative exposed, PCR-positive asymptomatic, and PCR positive with clinical signs); and 3) estimate individual heterogeneity in TB susceptibility, defined here as the time between TB exposure and detection, and survival after TB detection. We found that the TB detection probability once meerkats developed clinical signs was 13% (95% confidence interval 3-46%). Nevertheless, with an adapted test protocol of 10 PCR replicates per sample we detected hidden TB infections in 59% of meerkats before the onset of clinical signs. Meerkats became PCR positive approximately 14 mo after initial exposure, developed clinical signs approximately 1 yr after becoming PCR positive, and died within 5 mo of developing clinical signs. Individual variation in disease progression was high, with meerkats developing clinical signs from immediately after exposure to 3.4 yr later. Overall, our study generates novel insights into wildlife TB progression, and may help guide adapted management strategies for TB-susceptible wildlife populations.

Association between TAP gene polymorphisms and tuberculosis susceptibility in a Han Chinese population in Guangdong

Tuberculosis (TB) is an important public health problem. Studies indicated that TAP plays a key role in the presentation and transport of antigenic peptides during anti-M.tb infection. Given the important biological role of the TAP gene involved in anti-M.tb infection, a family-based case–control study including 133 tuberculosis patients, 107 healthy household contacts, and 173 healthy controls was conducted to assess the association between TAP gene polymorphisms and TB susceptibility. The basic information of subjects and their blood samples were collected. Four SNPs including rs1135216, rs1057141, rs241447, and rs3819721 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP). Our results suggested that BMI, residence, bedroom crowding, indoor humidity, fitness activities, history of smoking, and TB exposure history were associated with the occurrence of tuberculosis (P < 0.05). A significant association was observed between the TAP1 rs1135216 CT/CC genotype and increased TB risk, and the ORs were 2.56 (95% CI 1.31–4.99) and 6.73 (95% CI 1.33–34.02), respectively. TAP2 rs3819721 GG genotype carriers also showed an increased risk of TB when compared TB patients to healthy household contacts. Haplotype analysis revealed that the haplotype CT at rs1057141 and rs1135216 (OR = 11.34, 95% CI 1.49–86.56; OR = 7.45, 95% CI 1.43–38.76), as well as TA at rs241447 and rs3819721 (OR = 2.20, 95% CI 1.07–4.56) had a significantly increased risk of TB. The genetic risk scores (GRS) analysis of the four loci indicated that the risk of tuberculosis increased with increasing GRS scores in TB vs HHC (Ptrend = 0.010) and in TB vs HC (Ptrend = 0.001). In conclusion, our findings suggested that the SNPs of rs1135216 and rs3819721 were associated with TB susceptibility among the tuberculosis-prone families in the Chinese Han population and the risk of developing tuberculosis increases with the number of risk alleles, which could help identify high-risk groups in time and take scientific preventive measures. Further cohort studies with large samples are needed to validate the role of TAP gene variants on TB susceptibility.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00438-022-01885-3.

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

BackgroundThe 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. MethodsThis study included a cohort of 489 PTB patients and 489 healthy controls, and six SNPs were genotyped by improved multiple ligase detection reaction (iMLDR). ResultsWe 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). ConclusionsLEP 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.

REL and BHLHE40 Variants Are Associated with IL-12 and IL-10 Responses and Tuberculosis Risk.

The major human genes regulating Mycobacterium tuberculosis-induced immune responses and tuberculosis (TB) susceptibility are poorly understood. Although IL-12 and IL-10 are critical for TB pathogenesis, the genetic factors that regulate their expression in humans are unknown. CNBP, REL, and BHLHE40 are master regulators of IL-12 and IL-10 signaling. We hypothesized that common variants in CNBP, REL, and BHLHE40 were associated with IL-12 and IL-10 production from dendritic cells, and that these variants also influence adaptive immune responses to bacillus Calmette-Guérin (BCG) vaccination and TB susceptibility. We characterized the association between common variants in CNBP, REL, and BHLHE40, innate immune responses in dendritic cells and monocyte-derived macrophages, BCG-specific T cell responses, and susceptibility to pediatric and adult TB in human populations. BHLHE40 single-nucleotide polymorphism (SNP) rs4496464 was associated with increased BHLHE40 expression in monocyte-derived macrophages and increased IL-10 from peripheral blood dendritic cells and monocyte-derived macrophages after LPS and TB whole-cell lysate stimulation. SNP BHLHE40 rs11130215, in linkage disequilibrium with rs4496464, was associated with increased BCG-specific IL-2+CD4+ T cell responses and decreased risk for pediatric TB in South Africa. SNPs REL rs842634 and rs842618 were associated with increased IL-12 production from dendritic cells, and SNP REL rs842618 was associated with increased risk for TB meningitis. In summary, we found that genetic variations in REL and BHLHE40 are associated with IL-12 and IL-10 cytokine responses and TB clinical outcomes. Common human genetic regulation of well-defined intermediate cellular traits provides insights into mechanisms of TB pathogenesis.

Prevalence of Tuberculosis and Compliance to Treatment from 2010-2020 In Rivers State, Southsouth Nigeria

Tuberculosis is a highly contagious bacterial infection and it is still a leading killer of young adults worldwide. This study investigated the prevalence of tuberculosis and compliance to treatment from 2010 to 2020 in Rivers State, South-south Nigeria. The Ex-post factor design was utilized and it is aimed at collecting data and analyzing some variable retrospectively without manipulating any of the variables. Data were obtained from the Primary Healthcare Management Board and the State Ministry of Health covering a total of 525 (100%) healthcare facilities accounting for primary, secondary and tertiary health facilities including an overwhelming 191 (36.38%) private healthcare facilities. Data were analyzed using frequency and simple percentage including graphs. Findings inter alia reveals that the susceptibility and prevalence rate of Tuberculosis is higher in females than males, the highest prevalence rate of Tuberculosis in female (84.73%) was recorded in 2015 while that of the male (79.12%) occurred in 2016 respectively. The highest prevalence rate of Tuberculosis was 93.99% and it occurred in 2016 while the highest percentage compliance rate 48.99% was recorded in 2019. In addition, co-infections (TB/HIV) enhance the rate of Tuberculosis prevalence during the study period. Thus, it was recommended that effective awareness and sensitization campaign of the citizen via the churches, mosque, market unions, schools and anti-natal units among others on tuberculosis prevention and control be strengthened by all concerned agencies.

Diagnosis and Antimicrobial Susceptibility of Mycobacterium Tuberculosis in a Tertiary Care Hospital in Bangladesh

Background: Tuberculosis (TB) is a common condition all over the world but more common in developing countries like Bangladesh38. This is second only to HIV/AIDS as the greatest killer worldwide due to a single infectious agent. In 2013, 9 million people fell ill with TB and 1.5 million died from the disease globally. Approximately 15-20 % of total TB cases are extrapulmonary in non-HIV patients. Among extrapulmonary TB, abdominal tuberculosis (ATB) accounts for 11%-16%. Abdominal TB is difficult to diagnose because of its lack of specific symptoms, low yield of acid-fast bacilli (AFB) on smear and culture due to paucibacillary lesion; and variable manifestations depending upon anatomical localization of the disease. The diagnosis of abdominal TB classically requires histopathological, microbiological and culture confirmation of Mycobacterium tuberculosis. Investigations like Imaging (Ultrasound, Barium X-Rays, and CT scan) and the Mantoux test have only supportive value. Aim of the study: The aim of the study was to diagnose modalities and antimicrobial susceptibility in abdominal tuberculosis patients.Material &amp; Methods:This cross-sectional hospital-based observational study was carried out among 73 adult patients with the diagnosis of abdominal TB who met the selection criteria and attended in Gastroenterology department of DMCH through either admission or referral from May 2015 to April 2016.Results:The most frequent symptoms were weight loss (96.9%), abdominal pain (75%), and fever (75%). The most frequent signs were anaemia (34.4%), followed by ascites (27.9%). Basis of diagnosis in abdominal tuberculosis was histolopathogy in 37.5%, Gene Xpert in 28.1%, Positive AFB on culture in 9.4%, ADA value in ascitic fluid (Cutoff &gt;40 IU/L) in 25%, and good clinical response (Based on weight gain and general improvement in wellbeing) to a therapeutic trial of anti-TB treatment in 18.7% patients. Drug sensitivity pattern was analyzed in all three AFB culture-positive patients; resistance was detected in one which showed multidrug resistance (MDR TB).Conclusions:The result of this study highlighted the diagnostic yield of various investigation modalities, particularly newer modalities (Gene Xpert, culture sensitivity in Bactec MGIT 960) and basis of diagnosis in abdominal TB. This study also determined the MTB culture positivity from tissue biopsies in patients with abdominal TB and demonstrated drug-resistant MTB in culture-confirmed abdominal TB.

Expression of Vitamin D Receptor (VDR) gene and VDR polymorphism rs11574113 in pulmonary tuberculosis patients and their household contacts

The vitamin D receptor mediates the effect of vitamin D, which has received substantial attention in its involvement in reducing the risk of tuberculosis (TB). This study sought to see if VDR gene expression and VDR SNP rs11574113 was linked to a person's likelihood of developing tuberculosis. New Pulmonary Tuberculosis (PTB) VDR gene expression and Household Contact (HC) samples VDR gene expressions were examined by the quantitative real-time PCR (qPCR) method, while VDR SNP rs11574113 was identified by PCR followed by sequencing. Latent TB infection in household contacts was screened using an Interferon-Gamma Release Assay (IGRA). Eighty-three PTB, 77 HCs (45 positive-IGRA and 28 negative-IGRA) were involved in this study. Among the 45 positive-IGRA HC, 28 (62.2%) were spouses of index cases. IGRA results showed that 28 out of 37 (75.7%) samples of all spouses recruited have positive IGRA results. VDR gene expression of PTB was 0.2 and 0.25 downregulated compared to negative-IGRA and positive-IGRA HC, respectively (p = 0.014 and p = 0.011). VDR gene expression of positive-IGRA was also 0.788 downregulated compared to negative-IGRA HC but did not reach statistical significance (p = 0.945). The high expression of the VDR gene may be influenced by variant of VDR SNP rs11574113. G/G genotype and G/C genotype were associated with higher VDR gene expression compared to C/C genotype (ORa = 9.754 95% CI 1.482–64.195, p = 0.018 and ORa = 9.723 95% CI 1.416–66.751, p = 0.021, respectively). However, rs11574113 was not found to be associated with TB incidence and IGRA positivity. Approximately 20% of the people with PTB had higher levels of VDR gene expression than those who were not (ORa = 0.736 95% CI 0.542–0.998, p = 0.049). VDR gene expression may be associated with the susceptibility of tuberculosis. This study also shows an immense rate of TB infection among spouses of PTB patients based on IGRA.

Structural variability of Mycobacterium tuberculosis SSB and susceptibility to inhibition

Structural variability of Mycobacterium tuberculosis SSB and susceptibility to inhibition

Genetic Analysis of TB Susceptibility Variants in Ghana Reveals Candidate Protective Loci in SORBS2 and SCL11A1 Genes.

Despite advancements made toward diagnostics, tuberculosis caused by Mycobacterium africanum (Maf) and Mycobacterium tuberculosis sensu stricto (Mtbss) remains a major public health issue. Human host factors are key players in tuberculosis (TB) outcomes and treatment. Research is required to probe the interplay between host and bacterial genomes. Here, we explored the association between selected human/host genomic variants and TB disease in Ghana. Paired host genotype datum and infecting bacterial isolate information were analyzed for associations using a multinomial logistic regression. Mycobacterium tuberculosis complex (MTBC) isolates were obtained from 191 TB patients and genotyped into different phylogenetic lineages by standard methods. Two hundred and thirty-five (235) nondisease participants were used as healthy controls. A selection of 29 SNPs from TB disease-associated genes with high frequency among African populations was assayed using a TaqMan® SNP Genotyping Assay and iPLEX Gold Sequenom Mass Genotyping Array. Using 26 high-quality SNPs across 326 case-control samples in an association analysis, we found a protective variant, rs955263, in the SORBS2 gene against both Maf and Mtb infections (P BH = 0.05; OR = 0.33; 95% CI = 0.32–0.34). A relatively uncommon variant, rs17235409 in the SLC11A1 gene was observed with an even stronger protective effect against Mtb infection (MAF = 0.06; PBH = 0.04; OR = 0.05; 95% CI = 0.04–0.05). These findings suggest SLC11A1 and SORBS2 as a potential protective gene of substantial interest for TB, which is an important pathogen in West Africa, and highlight the need for in-depth host-pathogen studies in West Africa.

SLC11A1 genetic variation and low expression may cause immune response impairment in TB patients.

Tuberculosis (TB) is caused by Mycobacterium tuberculosis. Host genetic factors are important for the detection of TB susceptibility. SLC11A1 is located in monocyte phagolysosomes that help to limit M. tuberculosis growth by transferring divalent cations across the membrane. Genetic variation in SLC11A1 may alter its expression and increase the susceptibility of individuals to TB. The current study aimed to provide insight into host genetic variations and gene expression in TB patients. A total of 164 TB patients and 85 healthy controls were enrolled in this study. SLC11A1 polymorphisms were detected by PCR-RFLP. Real-time qPCR was used for SLC11A1 gene expression, and ELISA was used for protein estimation. GTEx Portal was used for quantitative trait loci analysis, while the STRING (v.11) web platform was used for gene interactive network construction. Data were analyzed using SPSS, GraphPad Prism, Haploview, and SNPstats. SLC11A1 polymorphisms and combinatorial genotypes were strongly associated with TB susceptibility, which may explain the greater prevalence of tuberculosis in the local population. Polymorphisms in SLC11A1 have also been linked to gene expression variation. Furthermore, the expression of SLC11A1 was downregulated in TB patients, which may influence the function of other associated genes and may impair the immunological response to tuberculosis.

Pulmonary tuberculosis susceptibility and association with Toll-Like receptor 2 Arg753Gln polymorphism.

Tuberculosis has been a concern of healthcare professionals due to the serious threats it poses on public health safety. However, regardless all the efforts, no appropriate goals for immunological diagnosis or tuberculosis treatment were established. Toll-like receptor 2 is one of the toll-like receptors, which plays a fundamental role in recognizing and hosting defense against Mycobacterium tuberculosis infection. Toll-like receptor 2's genetic polymorphism (arginine-to-glutamine substitution at residue 753 (Arg753Gln)) was linked to negative effects on the function of Toll-like receptor 2 which, in turn, impacts the body's resistance or susceptibility to tuberculosis. The current study aimed at investigating the single Arg753Gln nucleotide polymorphism of the Toll-like receptor 2 gene in patients with tuberculosis infection versus a sample of healthy subjects as controls. A comparative study was conducted to investigate Toll-like receptor 2 polymorphism of the single nucleotide gene Arg753Gln in 30 patients with pulmonary tuberculosis and compare their results with other 20 healthy controls matched by age and sex. TLR-2-Arg polymorphism allele A occurred in 36.7% of the patient group. Homozygous carriers of allele A/A polymorphism occurred in 13.4% compared to 5% among controls, while GA genotype was found in 23.3% among the study group and 10% among controls. The association between GA genotype and pulmonary tuberculosis was found statistically significant (p = 0.002) than other genotypes. Allele frequency for both G and A were (p =0.002) in patient groups and (p =0.000) among the control group. TLR-2 Arg753Gln polymorphisms may have a crucial role in pulmonary tuberculosis susceptibility among Egyptian patients.

Pleiotropic Effect of IL-6 Produced by B-Lymphocytes During Early Phases of Adaptive Immune Responses Against TB Infection.

The role of B cells migrating to the lung and forming follicles during tuberculosis (TB) inflammation is still the subject of debate. In addition to their antibody production and antigen-presenting functions, B cells secrete different cytokines and chemokines, thus participating in complex networks of innate and adaptive immunity. Importantly, lung B-cells produce high amounts of the pleiotropic gp130 cytokine IL-6. Its role during TB infection remains controversial, partly due to the fact that IL-6 is produced by different cell types. To investigate the impact of IL-6 produced by B cells on TB susceptibility and immune responses, we established a mouse strain with specific IL-6 deficiency in B cells (CD19cre-IL-6fl/fl, B-IL-6KO) on the B6 genetic background. Selective abrogation of IL-6 in B cells resulted in shortening the lifespan of TB-infected B-IL-6KO mice compare to the wild-type controls. We provide evidence that at the initial TB stages B cells serve as a critical source of IL-6. In the lung, the effect of IL-6 deficiency in B cells is associated rather with B and T cell functioning, than with macrophage polarization. TB-infected B-IL-6KO mice displayed diminished sizes of B cells themselves, CD4+IFN-γ+, Th17+, and CD4+CXCR5+ follicular T cell populations. The pleiotropic effect of B-cell-derived IL-6 on T-cells demonstrated in our study bridges two major lymphocyte populations and sheds some light on B- and T-cells interactions during the stage of anti-TB response when the host switches on a plethora of acquired immune reactions.

Performance Comparison of GeneXpert MTB/RIF, Gene Chip Technology, and Modified Roche Culture Method in Detecting Mycobacterium tuberculosis and Drug Susceptibility in Sputum.

Our aim of this study was to observe and analyze the performance of the real-time fluorescence quantitative nucleic acid amplification detection of Mycobacterium tuberculosis/rifampicin resistance (GeneXpert MTB/RIF), gene chip technology, and modified Roche culture method in detecting MTB in sputum submitted for inspection and drug susceptibility. Patients with smear-negative suspected pulmonary TB (n = 120) in our hospital were enrolled in this study using a random number table, and sputum samples submitted for inspection were tested by the GeneXpert MTB/RIF, gene chip technology, and modified Roche culture method. With clinical diagnosis as the gold standard, the performance (mainly sensitivity and specificity) of the above three detection methods in the diagnosis of MTB was compared. Next, the drug susceptibility test (DST) was carried out on sputum samples, tested positive by the three methods. With the solid culture results as the evaluation criteria, the performance of the three detection methods in the diagnosis MTB and DST was compared. When compared with the modified Roche culture method, the GeneXpert MTB/RIF had the highest positive rate and a shorter overall test duration (P < 0.05). In contrast with the gene chip technology, the GeneXpert MTB/RIF exhibited higher sensitivity and negative predictive value (NPV) and lower specificity, accuracy, positive predictive value (PPV), and Kappa value (P < 0.05). According to analysis of the diagnostic performance of the three detection methods, GeneXpert MTB/RIF displayed the highest diagnostic sensitivity, ideal predictive values, and the highest similarity with clinical diagnosis in results (P < 0.05). The detection of susceptibility to isoniazid (INH) and RIF showed that the GeneXpert MTB/RIF and gene chip technology performed ideally in DST of MTB. In comparison with the modified Roche culture method, the GeneXpert MTB/RIF and gene chip technology have more prominent performance in detecting MTB and drug susceptibility. Besides, to further improve the accuracy of clinical diagnosis, various molecular biology detection methods can be combined to avoid delaying of the best time for the diagnosis and treatment of the disease.

Delayed HIV treatment, barriers in access to care and mortality in tuberculosis/HIV co-infected patients in Cali, Colombia

Objective: To determine factors associated with mortality in tuberculosis/HIV co-infected patients in Cali, Colombia Methods: This retrospective cohort design included tuberculosis/HIV co-infected persons. Kaplan-Meier and Cox regression were used to estimate survival and risk factors associated with mortality. Results: Of the 279 tuberculosis/HIV co-infected participants, 27.2% died during the study. Participants mainly were adults and males. CD4 count information was available for 41.6% (the median count was 83 cells/mm3), and half were subject to tuberculosis susceptibility testing. The median time between HIV diagnosis and antiretroviral therapy initiation was 372 days. HIV was identified prior to tuberculosis in 53% and concurrent HIV-tuberculosis were diagnosed in 37% of patients. 44.8% had tuberculosis treatment success. Body mass index above 18 kg/m2, initiation of tuberculosis treatment within two weeks, having any health insurance coverage and CD4 count information conferred a survival advantage. Conclusions: Delays in treatment initiation and factors associated with limited health care access or utilization were associated with mortality. As HIV and tuberculosis are both reportable conditions in Colombia, strategies should be focused on optimizing treatment outcomes within both tuberculosis and HIV programs, particularly improving early HIV diagnosis, early antiretroviral therapy treatment initiation, and adherence to tuberculosis treatment.

Immune and inflammation-related gene polymorphisms and susceptibility to tuberculosis in Southern Xinjiang population: A case-control analysis.

Genetic and immune factors play an important role in tuberculosis. Under different ethnicities and genetic backgrounds, different immune and inflammation-related gene polymorphisms may confer different susceptibility to tuberculosis. This study investigated the relationship between immune and inflammation-related gene polymorphism and susceptibility to tuberculosis in Xinjiang Uyghur population, China. In this case-control study, we enrolled 507 pulmonary tuberculosis patients and 454 healthy controls from Southern Xinjiang. single nucleotide polymorphism (SNP) genotyping was performed. The 12 SNPs of nine immune and inflammation-related genes (including TNF rs361525, IL6 rs2066992 and rs1524107, IL17A rs3748067, IL17F rs763780, VDR rs731236, rs2228570 and rs1544410, IFNGR1 rs1327474, P2RX7 rs3751143, CTAGE1 rs4331426 and Toll-like receptor 4 (TLR4) rs4986790) and their relationship with tuberculosis were evaluated. The T allele and TT genotype of IL-6 rs2066992 and rs1524107 increased the risk of active tuberculosis. The C allele of IFNGR1 rs1327474 was related to the reduced risk of tuberculosis in the Xinjiang Uyghur population. The G allele and AG/GG genotypes of TLR4 rs4986790 were associated with an increased risk of tuberculosis (p<.05). Furthermore, haplotype analysis found that the haplotype TT of interleukin (IL)-6 was a risk factor, whereas the CG type was a protective factor for active tuberculosis in the Xinjiang Uyghur population. There were three immune and inflammation-related genes (IL-6, IFNGR1 and TLR4) and a total of four SNPs (rs2066992, rs1524107, rs1327474 and rs4986790) related to the susceptibility of the Uyghur population to tuberculosis. Our findings may provide evidence for further understanding the mechanism of tuberculosis susceptibility in the Xinjiang Uyghur population.

Role of Interferon-Gamma +874 A/T Single-Nucleotide Polymorphism and Tuberculosis Susceptibility of Pediatric Population in North Sumatera, Indonesia

BACKGROUND: Tuberculosis (TB) remains to be a leading cause of morbidity and mortality worldwide. The immune defense against Mycobacterium tuberculosis (M. tuberculosis) is complicated. Interferon gamma (IFN-g) is the main cytokine involved in the immune response of TB. To date, the role of +874 A/T single nucleotide polymorphism (SNP) and TB disease susceptibility continue to be controversial.&#x0D; OBJECTIVES: The aim of this study was to investigate the role of +874 A/T SNP and TB disease susceptibility of pediatric population in North Sumatera, Indonesia&#x0D; METHODS: A case control study was conducted in Medan and Batubara, North Sumatera, Indonesia from January to December 2016. A total of 51 children with TB and 51 healthy controls were enrolled in this study. Subjects were 2 months to 14 years old age children diagnosed with TB and written informed consent from the parents or the caregivers to participate. Subjects were withdrawn from the study when immunodeficiency condition was found or suffered from other infection disease. DNA samples were obtained from all of the subjects. +874 A/T SNP was identified by performing the amplification refractory mutational system - polymerase chain reaction (ARMS-PCR) method. IFN-g levels were measured by using human enzyme-linked immunosorbent assay/ELISA. Data analysis was performed using chi square and Mann Whitney test. p value &lt;0.05 was considered significant.&#x0D; RESULTS: The result of this study reveals the presence of AA, AT and TT genotype in TB patients were 31 (60.8%), 20 (39.2%) and 0 (0%); respectively (p=0.023). Significant decreased production of IFN-g levels (p=0.042) were found in TB patients 9.41 (1.10 – 28.06) pg/ml.&#x0D; CONCLUSION: Our study demonstrated significant evidence of the role of +874 A/T SNP and TB disease susceptibility of pediatric population in North Sumatera, Indonesia predominantly AA genotype. Significant decreased production of IFN-g reported among pediatric TB.

Genetic diversity and drug susceptibility of Mycobacterium tuberculosis in a city with a high prevalence of drug resistant tuberculosis from Southeast of Mexico

BackgroundMexico is on the top five countries with the highest number of TB cases in America continent, nevertheless, information about genotypes circulating is practically unknown. Considering the above this study aims to characterize the genetic diversity of TB in the city of Veracruz, México.MethodsA cross-sectional study was conducted among positive smear samples from patients living in Veracruz City, samples were cultured, and first-line drug profiles determined. Genotyping was made by spoligotyping and MIRU-VNTR 24 loci. Associations of lineages, clusters, and variables were also analyzed.ResultsAmong the 202 isolates analyzed resistance to at least one drug was observed in 60 (30%) isolates and 41(20%) were multidrug-resistant. Three major lineages were identified: L4/Euro-American (88%), L1/Indo-Oceanic (9%), and L2/East Asian (3%). The Euro-American lineage included more than six sublineages, the most abundant were: H (32%), T (23%), LAM (18%), and X (12%). 140 isolates (70%) were placed in 42 SITs patterns.ConclusionsThese results provide the first baseline data on the genetic structure of TB in the city of Veracruz. Sublineages H, X and LAM were predominant; however, it was founded an important diversity of genotypes that could contribute to the dispersion of TB and explain the high prevalence. This information might be useful for the development of further interventions to reduce impact of TB.

CYP2C8 and CYP2E1 genetic variants increase risk of tuberculosis in northwest Chinese Han population.

Tuberculosis (TB) is a chronic infectious disease which remains a main cause of death worldwide, and arises more and more concerns in recent years. CytochromeP450 (CYP450) is involved in the metabolism of many exogenous and endogenous compounds, and its polymorphism is associated with many diseases. The objective of our study was to explore the relationship between CYP450 polymorphisms and TB susceptibility in Northwest Chinese Han population. 506TB patients and 506 controls were recruited for our study, and their DNA were extracted. Six single nucleotide polymorphisms (SNPs) were selected for genotype. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated to evaluate the correlation between SNPs and TB risk. The genotype "TA" of CYP2C8 rs2275620 was related to an increased risk of TB in the co-dominant model (OR=1.33, 95%CI =1.00-1.76, p=0.049). In females, CYP2E1 rs2070672 was related to an increased TB susceptibility (co-dominant: OR=1.62, 95%CI=1.04-2.52, p=0.032; dominant: OR=1.66, 95%CI=1.08-2.56, p=0.020; additive: OR=1.60, 95%CI=1.08-2.36, p=0.018), and CYP2E1 rs2515641 was also associated with an increased risk of TB (co-dominant: OR=1.90, 95%CI=1.19-3.04, p=0.007; dominant: OR=1.94, 95%CI=1.23-3.05, p=0.004; additive: OR=1.80, 95%CI=1.20-2.71, p=0.005) in women. But there was no statistical significance between haplotypes and TB risk (p>0.05). Our research showed CYP2C8 and CYP2E1 polymorphisms are associated with an increased risk of TB in Northwest Chinese Han population, which may provide a crucial help on defining new therapeutic strategies for chemoprevention.

Association of Vitamin D Receptor Polymorphism (rs2228570, rs1544410, rs7975232, and rs731236) and Macrophage Migration Inhibitory Factor -173 G/C (rs755622) with the Susceptibility of Active Pulmonary Tuberculosis in Makassar, Indonesia

BACKGROUND: The study of Vitamin D Receptor (VDR) and Macrophage Migration Inhibitory Factor (MIF) polymorphisms, associated with active pulmonary tuberculosis (ATB) presents varying results. AIMS: This study aimed to investigate the association between VDR rs2228570, rs1544410, rs7975232, rs731236 and MIF -173 G/C (rs755622) single nucleotide polymorphism (SNP), with susceptibility of developing ATB, and positivity of Interferon Gamma Release Assay (IGRA) results (in household contact). METHODS AND MATERIAL: This study involved 83 ATB and 73 household contacts in Makassar. We checked IGRA based on ELISA in household contacts by using QuantiFERON TB Gold Plus test, and we found that 61.64% (n = 45) of household contacts had positive IGRA. Polymorphism examination was carried out by Sanger sequencing. RESULTS: VDR rs2228570 T/T and T/C-T/T were significantly associated with higher risk of active tuberculosis. VDR rs7975232 G/G genotype was associated with an increased risk of developing active TB compared to T/T-T/G. Haplotype analysis of VDR rs2228570, rs1544410, rs7975232, rs731236 and combination with MIF rs755622 demonstrated that TGGTG was observed to have a higher risk of tuberculosis. CONCLUSIONS: The combination of VDR and MIF variants may contribute to the susceptibility of active tuberculosis disease.