PURPOSE: Numerous studies have assessed the association of SP110 gene variants with tuberculosis (TB), but the results were inconsistent. Through a comprehensive review and meta-analysis, our study aimed to clarify the nature of genetic risks contributed by 11 polymorphisms for the development of TB. MATERIALS AND METHODS: Through searching PubMed, web of science, China National Knowledge Infrastructure (CNKI) databases, a total of 11 articles including 13 independent studies were selected. The pooled odd ratios (ORs) along with their corresponding 95% confidence interval (CI) were estimated for allelic comparisons, additive model (homozygote comparisons; heterozygote comparisons), dominant model and recessive model. We also assessed the heterogeneity across the studies and publication bias. RESULTS: The results of combined analysis revealed a significantly increased risk of TB for single nucleotide polymorphism (SNP) rs9061 in all five comparisons (allelic comparisons: OR=1.28, 95% CI=1.14–1.44, p<0.0001; homozygote comparisons: OR=2.84, 95% CI=1.84–4.38, p<0.00001; heterozygote comparisons: OR=1.23, 95% CI=1.05–1.43, p=0.009; dominant model: OR=1.32, 95% CI=1.14–1.53, p=0.0003; recessive model: OR=2.26, 95% CI=1.18–4.34, p=0.01). In subgroup analysis, the risk of TB associated with SNP rs9061 appeared to be increased. Moreover, increased risk of TB was also found in Asian subgroup of SNP rs11556887, while decreased risk of TB appeared in large sample size subgroup of SNP rs1135791. No significant association was observed between other SNPs and the risk of TB. CONCLUSION: Our meta-analysis suggested that the variant of SNP rs9061 might be a risk factor for TB.
Alleles ; Asian Continental Ancestry Group/genetics ; China ; Confidence Intervals ; Genetic Predisposition to Disease ; Heterozygote ; Homozygote ; Humans ; Minor Histocompatibility Antigens/*genetics ; Nuclear Proteins/*genetics ; Odds Ratio ; *Polymorphism, Single Nucleotide ; Risk Factors ; Tuberculosis, Pulmonary/*genetics

Pharmacogenetic testing for clinical applications is steadily increasing. Correct and adequate use of pharmacogenetic tests is important to reduce unnecessary medical costs and adverse patient outcomes. This document contains recommended pharmacogenetic testing guidelines for clinical application, interpretation, and result reporting through a literature review and evidence-based expert opinions for the clinical pharmacogenetic testing covered by public medical insurance in Korea. This document aims to improve the utility of pharmacogenetic testing in routine clinical settings.
Anticoagulants/therapeutic use ; Antidepressive Agents/therapeutic use ; Antimetabolites, Antineoplastic/therapeutic use ; Antitubercular Agents/therapeutic use ; Arylamine N-Acetyltransferase/genetics ; Coronary Artery Disease/drug therapy/genetics ; Cytochrome P-450 CYP2C19/genetics ; Cytochrome P-450 CYP2C9/genetics ; Cytochrome P-450 CYP2D6/genetics ; Depressive Disorder/drug therapy/genetics ; Genotype ; Isoniazid/therapeutic use ; Laboratories, Hospital/standards ; Methyltransferases/genetics ; Pharmacogenomic Testing/*methods/standards ; Platelet Aggregation Inhibitors/therapeutic use ; Pulmonary Embolism/drug therapy/genetics ; Ticlopidine/analogs & derivatives/therapeutic use ; Tuberculosis/drug therapy/genetics ; Vitamin K Epoxide Reductases/genetics ; Warfarin/therapeutic use

A case-control study was carried out that involved 203 individuals diagnosed with pulmonary tuberculosis (PTB) and 203 healthy subjects. Genotyping of TLR1 rs5743551 and rs5743618 polymorphisms was done using polymerase chain reaction-restriction fragments length polymorphism assay. We found that TLR1 rs5743551 variant affected the risk of PTB in the codominant (OR=3.28, 95% CI=1.98-5.45, P<0.0001, GA vs. GG; OR=1.86, 95% CI=1.05-3.28, P=0.033, AA vs. GG) and dominant (OR=2.69, 95% CI=1.67-4.34, P<0.0001, GA+AA vs. GG) inheritance models tested. The A allele was associated with a higher risk of PTB than the G allele (OR=1.33, 95% CI=1.01-1.75, P=0.049). The TG genotype of the rs5743618 variant significantly increased the risk of PTB compared to the risk associated with the TT genotype (OR=3.29, 95% CI=1.82-5.97, P<0.0001). The G allele was associated with a higher risk of PTB than the T allele (OR=3.00, 95% CI=1.69-5.31, P=0.0001). Our findings revealed that TLR1 rs5743551 and rs5743618 polymorphisms affected the risk of PTB in an Iranian population sample. Additional studies with larger sample sizes and involving subjects of different ethnicities are required to validate our present findings.
Adult ; Case-Control Studies ; Female ; Humans ; Iran ; epidemiology ; Male ; Middle Aged ; Polymorphism, Genetic ; Risk Factors ; Toll-Like Receptor 1 ; genetics ; Tuberculosis, Pulmonary ; epidemiology ; genetics

We evaluate the performance of Xpert MTB/RIF for the diagnosis of extrapulmonary tuberculosis (EPTB) in China. The performance of Xpert was evaluated compared to the composite reference standard (CRS), drug susceptibility testing (DST), and imaging examination. The overall sensitivity and specificity of Xpert were 64.1% (195/304) and 100% (24/24), respectively, using CRS as the gold standard. The sensitivity was significantly higher than that of culture for pus (P<0.05). The proportion of EPTB-positive cases diagnosed by imaging was two times more than that diagnosed using Xpert; however, 6 out of 19 cases may have been overdiagnosed by imaging. Compared to phenotypic DST, the sensitivity and specificity of Xpert were 80% (12/15) and 100% (75/75), respectively. Considering its high sensitivity and specificity, Xpert MTB/RIF may be used as a rapid initial test for EPTB diagnosis, and may also support a quicker decision on the treatment regimen. The combination of imaging and Xpert testing could provide high efficiency and accurate diagnosis of suspected EPTB.
Bacterial Proteins ; genetics ; metabolism ; China ; DNA-Directed RNA Polymerases ; genetics ; metabolism ; Diagnostic Tests, Routine ; instrumentation ; methods ; Drug Resistance, Bacterial ; Humans ; Microbial Sensitivity Tests ; Mycobacterium tuberculosis ; drug effects ; genetics ; isolation & purification ; metabolism ; Retrospective Studies ; Rifampin ; pharmacology ; Sensitivity and Specificity ; Sputum ; Tuberculosis ; Tuberculosis, Pulmonary ; diagnosis ; microbiology

OBJECTIVEThe effect of rs4331426 polymorphism in the Chr18q11.2 locus on pulmonary tuberculosis (PTB) risk was evaluated.

METHODSThis case-control study included 208 PTB patients and 204 healthy subjects. Genotyping of the rs4331426 variant was conducted using polymerase chain reaction restriction fragment length polymorphism.

RESULTSThe frequencies of genotypes AA, AG, and GG polymorphisms were 83.1%, 15.9%, and 1.0% in the PTB group and 84.3%, 15.2%, and 0.5% in the control group, respectively. The frequency of the minor (G) allele was 8.9% in the PTB group and 8.1% in controls. Neither genotype nor allele frequencies of the rs4331426 variant showed statistically significant differences between PTB and controls. In addition, stratification by sex showed no significant association between the rs4331426 variant and PTB risk in males or females.

CONCLUSIONIn conclusion, the results of this study do not support an association between the rs4331426 polymorphism and risk of PTB in an Iranian population.

Adult ; Aged ; Case-Control Studies ; Chromosomes, Human, Pair 18 ; genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Iran ; epidemiology ; Male ; Middle Aged ; Polymorphism, Genetic ; Tuberculosis, Pulmonary ; epidemiology ; genetics

OBJECTIVETo assess the association of copy number variations (CNVs) of exon 11 of IL-23 receptor gene with susceptibility to active pulmonary tuberculosis among Chinese Uygurs.

METHODSIn this study, 250 subjects with active pulmonary tuberculosis (PTB) and 250 normal controls were recruited. A paired case-control study was conducted in the Chinese Uygur population in Xinjiang and the CNV of IL-23R was analyzed using Taqman real-time PCR.

RESULTSThe study showed that the frequencies of different copy number in exon 11 of IL-23R between PTB and control groups were statistically significant (χ(2)=13.35, P<0.01). There were significant difference in CNV of exon 11 in IL-23R between PTB patients and controls (χ(2)=14.95, P<0.01, OR=2.875, 95%CI: 1.655-4.994). The increase of copy number in exon 11 of IL-23R showed significantly different between PTB and control groups (χ(2)=10.475, P=0.0012, OR=2.611, 95%CI: 1.437-4.744).

CONCLUSIONThe CNV of exon 11 in IL-23R is associated with PTB in the Chinese Uygur population. The increase of the copy number in exon 11 of IL-23R may be a risk factor for PTB in Chinese Uygurs.

Adult ; Aged ; Asian Continental Ancestry Group ; ethnology ; genetics ; Case-Control Studies ; China ; ethnology ; DNA Copy Number Variations ; Exons ; Female ; Genetic Predisposition to Disease ; ethnology ; Humans ; Male ; Middle Aged ; Receptors, Interleukin ; genetics ; Tuberculosis, Pulmonary ; ethnology ; genetics ; Young Adult

The AdvanSure tuberculosis/non-tuberculous mycobacterium (TB/NTM) PCR (LG Life Science, Korea) and COBAS TaqMan Mycobacterium tuberculosis (MTB) PCR (Roche Diagnostics, USA) are commonly used in clinical microbiology laboratories. We aimed to evaluate these two commercial real-time PCR assays for detection of MTB in a large set of clinical samples over a two-year period. AdvanSure TB/NTM PCR and COBAS TaqMan MTB PCR were performed on 9,119 (75.2%) and 3,010 (24.8%) of 12,129 (9,728 respiratory and 2,401 non-respiratory) MTB specimens, with 361 (4.0%) and 102 (3.4%) acid-fast bacilli (AFB)-positive results, respectively. In MTB culture, 788 (6.5%) MTB and 514 (4.2%) NTM were identified. The total sensitivity and specificity of the AdvanSure assay were 67.8% (95% confidence interval [CI], 63.9-71.6) and 98.3% (95% CI, 98.0-98.6), while those of the COBAS TaqMan assay were 67.2% (95% CI, 60.0-73.8) and 98.4% (95% CI, 97.9-98.9), respectively. The sensitivities and specificities of the AdvanSure and COBAS TaqMan assays for AFB-positive and AFB-negative samples were comparable. Furthermore, the AdvanSure assay showed fewer invalid results compared with the COBAS TaqMan assay (5.0 vs. 20.4 invalid results/1,000 tests, P<0.001). AdvanSure assay represents a comparable yet more reliable method than COBAS TaqMan for the identification of mycobacteria in routine clinical microbiology.
DNA, Bacterial/genetics/metabolism ; Humans ; Mycobacterium tuberculosis/*genetics/isolation & purification ; Reagent Kits, Diagnostic ; Real-Time Polymerase Chain Reaction ; Republic of Korea ; Sensitivity and Specificity ; Tuberculosis, Pulmonary/diagnosis

BACKGROUNDEarly detection of pulmonary tuberculosis (PTB) is a big challenge in smear negative and sputum scarce patients in China. Simultaneous amplification and testing methods for detection of the Mycobacterium tuberculosis (MTB) complex (SAT-TB assay) is a novel molecular technique established in our hospital. This method has a high sensitivity and specificity in the lab. In this study, the clinical diagnostic performance of this method in smear-negative or sputum-scarce PTB suspects was investigated and evaluated.

METHODSTwo hundred smear negative and 80 sputum-scarce patients were recruited in this study. Samples that included sputum or bronchial washing fluid were collected and sent for both bacteria culture and SAT-TB assay. Diagnosis for these patients was based on the comprehensive evaluation of chestX- ray/CT study, histology examination, lab results, and treatment response. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for each diagnostic test were investigated and calculated using confirmed tuberculosis (TB) and non-TB cases. The time required for detection of MTB was also measured for each method.

RESULTSNinety-two patients (33%) were diagnosed as definitive TB, 112 patients (40%) were probable PTB, and 76 (27%) were non-TB. The sensitivity, specificity, PPV, and NPV of SAT-TB in smear-negative PTB suspects were 93% (95% CI, 84%-98%), 98% (95% CI, 90%-100%), 98% (95% CI, 91%-100%), and 93% (95% CI, 83%-98%). In sputum scarce PTB suspects, the sensitivity, specificity, PPV, and NPV of the SAT-TB assay on bronchial washing fluids were 90% (95% CI, 74%-98%), 100% (95% CI, 85%-100%), 100% (95% CI, 88%-100%), and 88% (95% CI, 69%-97%). The accuracy of the SAT-TB assay is consistent with the bacteria culture assay. The median time required for detecting MTB in the SAT-TB assay was 0.5 day, which was much faster than bacteria culture (28 days).

CONCLUSIONSThe SAT-TB assay is a fast and accurate method for the detection of MTB. It can be widely applied in the clinic and be an asset in early detection and management of PTB suspects, especially in those patients who are smear negative or sputum scarce.

Adult ; China ; Female ; Humans ; Male ; Middle Aged ; Mycobacterium tuberculosis ; genetics ; pathogenicity ; Nucleic Acid Amplification Techniques ; methods ; Sputum ; microbiology ; Tuberculosis, Pulmonary ; diagnosis ; Young Adult

OBJECTIVETo investigate the feasibility of real-time fluorescent quantitative (qPCR) assay in detecting mycobacterium tuberculosis complex (MTB) in paraffin embedded tissues for diagnostic purpose.

METHODSUsing qPCR assay, 1000 consecutive formalin-fixed and paraffin embedded (FFPE) tissues (from 2011 to 2012) suspected of MTB infection were tested by amplifying the MTB specific insertion sequence 6110 (IS6110). The specificity of the PCR product was confirmed by Sanger sequencing as compared with the MTB genomic DNA of the IS6110 sequence. Tissues with Ziehl-Neelsen acid-fast staining were used as control.

RESULTSIn the 1000 samples, 513 were positive for mycobacterium by Ziehl-Neelsen acid-fast staining (detection rate 51.3%); whereas 546 were MTB positive by qPCR assay (detection rate 54.6%). Concordance rate for both assays was 73.1%. The diagnosis rate increased by 14.4% by combinination of Ziehl-Neelsen acid-fast staining and qPCR results. More interestingly, by analyzing the Ziehl-Neelsen acid-fast staining and qPCR results three cases of M.leprae infection and four cases of non-tuberculous Mycobacterium (NTM) infection were identified.

CONCLUSIONSqPCR detection of MTB in FFPE tissue is more sensitive than Ziehl-Neelsen acid-fast staining assay. Combination of these two assays can increase the detection rate and also identify some rare cases of NTM infection.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; DNA, Bacterial ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mycobacterium tuberculosis ; genetics ; isolation & purification ; Paraffin Embedding ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; Staining and Labeling ; methods ; Tuberculosis ; diagnosis ; microbiology ; Tuberculosis, Gastrointestinal ; diagnosis ; microbiology ; Tuberculosis, Lymph Node ; diagnosis ; microbiology ; Tuberculosis, Pulmonary ; diagnosis ; microbiology ; Young Adult

OBJECTIVETo investigate the possible association between the SNP in the 5' untranslated region (5' UTR) of the human beta defensin 1 (DEFB1) gene and the susceptibility to pulmonary tuberculosis (PTB) in Chinese Han population.

METHODSIn this case-control study, venous blood was collected from 102 patients with PTB and 148 healthful persons. Genomic DNA was extracted using whole blood DNA extraction kit. The -52A/G, -44C/G and -20A/G SNP were genotyped by PCR-directed sequencing. The genotypes and allele frequency were analyzed using the χ(2) test. The linkage disequilibrium and haplotype were analyzed by SHEsis software.

RESULTSA total of 102 patients with PTB (69 males and 33 females, (53.42 ± 20.22) years old) and 148 healthy control cases (95 males and 53 females, (50.67 ± 14.53) years old) were enrolled, with no difference in gender and age (all P values > 0.05). DEFB1 -44 CC genotype was significantly more frequently found in PTB patients than in control group (81.4% (83/102) vs 66.9% (99/148), χ(2) = 5.114, P < 0.05, OR = 2.096, 95%CI: 1.095 - 4.011), so was -44C allele (89.2% (182/204) vs 80.4% (238/296), χ(2) = 6.975, P < 0.05, OR = 1.576, 95%CI: 1.086 - 2.286). No difference in -52 A/G and -20 A/G SNP was observed between the two groups. The proportion of the GGG (-52/-44/-20) haplotype was lower in PTB patients than in the control group (0.030 vs 0.081, χ(2) = 5.629, P < 0.05, OR = 0.348, 95%CI: 0.140 - 0.863). No linkage disequilibrium was found among the SNP of the three sites (D' values were 0.132, 0.064, 0.088; r(2) values were 0.003, 0.002, 0.003; all P values > 0.05).

CONCLUSIONThese results suggest that the SNP of DEFB1 5' UTR is associated with susceptibility to PTB in Chinese Han population. -44 C→G SNP and the related haplotype (GGG) might play a protective role in the pathogenesis of PTB.

Adult ; Aged ; Case-Control Studies ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Tuberculosis, Pulmonary ; genetics ; beta-Defensins ; genetics