Pulmonary Tuberculosis Susceptibility Research Articles

Association of Genetic Polymorphisms of IFNGR1 with the Risk of Pulmonary Tuberculosis in Zahedan, Southeast Iran.

Aim. The present study was undertaken to find out the possible association between interferon-gamma (IFN-γ) receptor 1 (IFNGR1) gene polymorphisms and risk of pulmonary tuberculosis (PTB) in a sample of Iranian population. Methods. Polymorphisms of IFNGR1 rs1327474 (−611 A/G), rs11914 (+189 T/G), rs7749390 (+95 C/T), and rs137854905 (27-bp ins/del) were determined in 173 PTB patients and 164 healthy subjects. Results. Our findings showed that rs11914 TG genotypes decreased the risk of PTB in comparison with TT (OR = 0.36, 95% CI = 0.21–0.62, and p = 0.0002). The rs11914 G allele decreased the risk of PTB compared with T allele (OR = 0.41, 95% CI = 0.25–0.68, and p = 0.0006). IFNGR1 rs7749390 CT genotype decreased the risk of PTB in comparison with CC genotype (OR = 0.55, 95% CI = 0.32–0.95, and p = 0.038). No significant association was found between IFNGR1 rs1327474 A/G polymorphism and risk/protective of PTB. The rs137854905 (27-bp I/D) variant was not polymorphic in our population. Conclusion. Our findings showed that IFNGR1 rs11914 and rs7749390 variants decreased the risk of PTB susceptibility in our population.

Association between vitamin D receptor polymorphisms and haplotypes with pulmonary tuberculosis.

The vitamin D receptor (VDR) is an important factor in activating immune response in different infectious diseases. The aim of the present study was to investigate the association between the VDR gene polymorphisms and pulmonary tuberculosis (PTB). The case control study was performed on 120 PTB patients and 131 healthy controls. Genetic analysis was performed by polymerase chain reaction and the restriction fragment length polymorphism method. The VDR Fok1 Ff genotype was associated with TB and the risk of PTB was two times higher in individuals with the Ff genotype. A higher frequency of f allele was observed in PTB patients and therefore, the f allele may be a risk factor for PTB susceptibility. There were no associations between the Taq1 and Bsm1 polymorphisms and PTB. In addition, haplotype analysis showed that the f-T-B and f-t-b haplotypes (Fok1, Taq1 and Bsm1) may have the potential to increase PTB susceptibility. In conclusion, the Ff genotype and f allele of the VDR Fok1 polymorphism were associated with PTB susceptibility. In addition, the f-T-B and f-t-b haplotypes may be the susceptible haplotypes for PTB.

Epiregulin (EREG) and human V-ATPase (TCIRG1): genetic variation, ethnicity and pulmonary tuberculosis susceptibility in Guinea-Bissau and The Gambia.

We analyzed two West African samples (Guinea-Bissau: n=289 cases and 322 controls; The Gambia: n=240 cases and 248 controls) to evaluate single-nucleotide polymorphisms (SNPs) in Epiregulin (EREG) and V-ATPase (T-cell immune regulator 1 (TCIRG1)) using single and multilocus analyses to determine whether previously described associations with pulmonary tuberculosis (PTB) in Vietnamese and Italians would replicate in African populations. We did not detect any significant single locus or haplotype associations in either sample. We also performed exploratory pairwise interaction analyses using Visualization of Statistical Epistasis Networks (ViSEN), a novel method to detect only interactions among multiple variables, to elucidate possible interaction effects between SNPs and demographic factors. Although we found no strong evidence of marginal effects, there were several significant pairwise interactions that were identified in either the Guinea-Bissau or the Gambian samples, two of which replicated across populations. Our results indicate that the effects of EREG and TCIRG1 variants on PTB susceptibility, to the extent that they exist, are dependent on gene-gene interactions in West African populations as detected with ViSEN. In addition, epistatic effects are likely to be influenced by inter- and intra-population differences in genetic or environmental context and/or the mycobacterial lineages causing disease.

A meta-analysis of P2X7 gene-762T/C polymorphism and pulmonary tuberculosis susceptibility.

AimWe performed a comprehensive meta-analysis to determine the association between P2X7 -762T/C polymorphism and pulmonary tuberculosis susceptibility.MethodologyBased on comprehensive searches of the PubMed, SCI, Elsevier, China National Knowledge Infrastructure (CNKI) and Wanfang Database, we identified eligible studies about the association between P2X7 -762T/C polymorphism and pulmonary tuberculosis risk. Pooled odds ratio (ORs) and 95% confidence intervals (95%CIs) were calculated in random-effects model.ResultsA total of 2207 tuberculosis cases and 2220 controls in 8 case-control studies were included in this meta-analysis. Allele model (C vs. T: p = 0.15; OR = 0.83, 95% CI = 0.65–1.07), homozygous model (CC vs. TT: p = 0.23; OR = 0.73, 95% CI = 0.44 to 1.22), and heterozygous model (CT vs. TT: p = 0.57; OR = 0.92, 95% CI = 0.68 to 1.24) did not show increased risk of developing pulmonary tuberculosis. Similarly, dominant model (CC+CT vs. TT: p = 0.32; OR = 0.84, 95% CI = 0.59 to 1.19) and recessive model (CC vs. CT+TT: p = 0.08; OR = 0.77, 95% CI = 0.57 to 1.04) failed to show increased risk of developing pulmonary tuberculosis. Subgroup analysis by ethnicity did not detect any significant association between P2X7–762T/C polymorphism and pulmonary tuberculosis susceptibility.Conclusions P2X7 -762T/C gene polymorphism is not associated with pulmonary tuberculosis susceptibility.

Genetic diversity of TLR2, TLR4, and VDR loci and pulmonary tuberculosis in Moroccan patients.

Toll-like receptors (TLRs) 2, 4, and the vitamin D receptor (VDR) are central components of the innate and adaptive immunity against Mycobacterium tuberculosis (Mtb). TLR2, TLR4, and VDR polymorphisms were previously associated with tuberculosis (TB) and were here investigated as candidates for pulmonary TB (PTB) susceptibility in a Moroccan population group. Genomic DNA from 343 PTB patients and 203 healthy controls were analyzed for 12 single nucleotide polymorphisms (SNPs) located in TLR2, TLR4, and VDR genes using polymerase chain reaction-based restriction fragment length polymorphism and TaqMan SNP genotyping assays. The TLR2 +597 CT genotype was associated with protection against PTB (corrected p [pc] = 0.04; odds ratio (OR) = 0.65; 95% confidence interval (CI) = 0.45 - 0.94), and the TLR4 +7263 C allele was significantly associated with PTB susceptibility (pc = 0.04; OR = 1.63; CI = 1.06 - 2.57). The VDR [f,b,a,T] haplotype was found to confer protection (pc < 0.00001; OR = 0.18; CI = 0.09 - 0.35), while the TLR2 [-16934T,+597C,+1349T] haplotype seemed to be at risk (p = 0.03; OR = 1.52; CI = 1.01 - 2.30), but statistical significance was not reached. Finally, cross-analysis between polymorphisms of the three studied genes revealed significant interaction between TLR2 +597 and TLR4 +4434 SNPs towards protection against PTB (pc = 0.036), suggesting that the functionally relevant TLR4 +4434 SNP may act synergistically with TLR2 SNPs. TLR2 and TLR4 interaction and a specific VDR haplotype influence protection against PTB in Moroccans patients.

No Evidence for Association Between the Functional rs1862513 Polymorphism in the Promoter Region of the Resistin Gene (RETN) and Pulmonary Tuberculosis in Northern Spain

Background: Elevated levels of circulating Resistin, a peptide hormone produced by adipocytes in rodents but also by monocytes and macrophages in humans, has been reported in patients with tuberculosis infection. To date, only a few studies mainly focused in conditions such as diabetes, obesity, and cardio-metabolic risk have treated to analyse the role of single nucleotide polymorphisms in the Resistin Gene (RETN). However, polymorphisms in this gene have not been previously tested in pulmonary tuberculosis susceptibility. Methods: The rs1862513 (-420C>G), a functional polymorphism in the RETN gene, which has been found to increase circulating resistin levels, was analysed in 192 patients with pulmonary tuberculosis, all of them HIV negative, and in 245 healthy individuals from a well genetically conserved Spanish population. Results: Significant differences in genotype and allele frequencies of the rs1862513 functional polymorphism were not observed between patients and normal controls. Conclusion: Our results would indicate that RETN rs1862513 would not play a major role in the susceptibility to pulmonary tuberculosis at least in our population in a well-powered study.

NOD2 Polymorphisms and Pulmonary Tuberculosis Susceptibility: A Systematic Review and Meta-Analysis

The association between NOD2 and tuberculosis (TB) risk has been reported widely, but the results of previous studies remained controversial and ambiguous. To assess the association between NOD2 polymorphisms and TB risk, a meta-analysis was performed. A literature search was conducted by using the PubMed, Ovid, ISI Web of Knowledge, Elsevier ScienceDirect, and Chinese National Knowledge Infrastructure (CNKI). We identified the data from all articles estimating the association between NOD2 polymorphisms and TB risk. In total, 2,215 cases and 1,491 controls in 7 case-control studies were included. In meta-analysis, we found significant association between the Arg702Trp polymorphism and TB risk (OR = 0.43, 95% CI = 0.20-0.90, P = 0.02). However, no significant association was found between the Arg587Arg (OR = 1.31, 95% CI = 0.83-2.07, P = 0.25) and Gly908Arg (OR = 0.78, 95% CI = 0.21-2.87, P = 0.71) polymorphisms and TB risk. The present meta-analysis suggested that NOD2 Arg702Trp polymorphism was likely to be a protective factor for TB. However, the Arg587Arg and Gly908Arg polymorphisms might not be the genetic risk factors for TB susceptibility.

Meta-Analysis on the Associations of TLR2 Gene Polymorphisms with Pulmonary Tuberculosis Susceptibility among Asian Populations

BackgroundPublications regarding the associations of toll-like receptor 2 (TLR2) G2258A and T597C polymorphisms with pulmonary tuberculosis (PTB) susceptibility are inconsistent. A meta-analysis was conducted to investigate the relationship between TLR2 G2258A and T597C polymorphisms with PTB susceptibility.MethodsA systematic search was performed for published studies on the relationship between TLR2 polymorphisms and PTB susceptibility. Information was gathered from each eligible study, and statistically analyzed.Results6 eligible studies, totaling 1301 cases and 1217 controls on G2258A genotypes, and 8 studies, totaling 2175 cases and 2069 controls on T597C genotypes, were included in the analysis. TLR2 2258G allele and 2258GG genotype were found to be associated with decreased PTB susceptibility (A vs. G: OR = 3.02, 95% CI: 2.22–4.12, P<0.001, GA+AA vs. GG: OR = 2.69, 95% CI = 1.49–4.87, P = 0.001). In the subgroup analyses, the 2258G allele and 2258GG genotype also exhibited a protective effect of PTB risk in Asians (A vs. G: OR = 2.95, 95% CI: 1.91–4.55, P<0.001; GA+AA vs. GG: OR = 3.59, 95% CI: 2.23–5.78, P<0.001), while no associations were observed in Caucasians. No significant associations between T597C polymorphism and PTB were found in the allele model (C vs. T: OR = 0.95, 95% CI: 0.86–1.04, P = 0.28), co-dominant model (CC vs. TT: OR = 0.88, 95% CI = 0.92–1.40, P = 0.25; CT vs. TT: OR = 0.92, 95% CI = 0.80–1.06, P = 0.28), recessive model (CC vs. TT+TC: OR = 0.96, 95% CI: 0.80–1.16, P = 0.69), or dominant model (TC+CC vs. TT: OR = 0.93, 95% CI = 0.76–1.15, P = 0.51). The associations of T597C polymorphism with PTB susceptibility, in the ethnic-specific analyses, were still not significant.ConclusionTLR2 2258G allele may provide protective effects against PTB susceptibility, particularly among Asians, whereas TLR2 T597C polymorphism might not be associated with PTB susceptibility.

Distribution of HLA-A, B and DRB1 alleles in Sahariya tribe of North Central India: An association with pulmonary tuberculosis

Sahariya, a primitive tribe, native of North Central India, is characterized by a significantly increased incidence of pulmonary tuberculosis (PTB) as compared to other tribes from the same region. Host genetic factors are known to influence susceptibility to PTB at the population level. Since an association of immune regulatory genes, particularly HLA, with PTB susceptibility has already been reported in several studies, we investigated a similar association of HLA alleles with PTB pathogenesis in the Sahariya tribe. A total of 210 cases and 178 healthy individuals from Sahariya tribe were genotyped for HLA class I and II alleles using the PCR based SSP and Reverse-SSO methods. The study showed a significantly increased allelic frequency of HLA-DRB1∗15 (p=0.02) in the patients as compared to healthy controls. However, the allelic frequency of HLA-DRB1∗16 was significantly reduced in patients than in controls (p=0.01). Three locus haplotype analysis of HLA-A, B and DR revealed a significantly increased frequency of A∗24-B∗40-DRB1∗15 haplotype among patients than controls (p=0.005), while A∗02-B∗40-DRB1∗16 and A∗02-B40-DRB1∗03 (p=0.001 and 0.02, respectively) were significantly reduced in the patients. Our findings confirm a positive association of HLA-DRB1∗15 in Sahariya tribe similar to the one already shown in other Indian ethnic groups. On the other hand, HLA-A∗24-B∗40-DRB1∗15 haplotype was found to be specific to Sahariya tribe with a strong predisposition to PTB. Further, the protection offered by DRB1∗16 allele and associated haplotypes towards PTB in this tribe appears to be a novel finding that warrants further investigation with regard to resistance to PTB.

Toll-Like Receptor -1, -2, and -6 Polymorphisms and Pulmonary Tuberculosis Susceptibility: A Systematic Review and Meta-Analysis

BackgroundA large number of studies have investigated whether polymorphisms in the Toll-like receptor (TLR) genes are implicated in susceptibility to tuberculosis (TB) in different populations. However, the results are inconsistent and inconclusive.MethodsA literature search was conducted using the PubMed, EMBASE, Medline (Ovid), ISI Web of Knowledge and Chinese National Knowledge Infrastructure (CNKI). A meta-analysis on the associations between the TLR1 G1805T, TLR2 T597C, T1350C, G2258A, and TLR6 C745T polymorphisms and TB risk was carried out by comparison using different genetic models.ResultsIn total, 16 studies from 14 articles were included in this review. In meta-analysis, significant associations were observed between the TLR2 2258AA (AA vs. AG+AG, OR 5.82, 95% CI 1.30–26.16, P = 0.02) and TLR6 745TT (TT vs. CT+CC, OR 0.61, 95% CI 0.39–0.97, P = 0.04) polymorphisms and TB risk. In the subgroup analysis by ethnicity, Africans and American Hispanic subjects with the TLR1 1805T allele had an increased susceptibility, whereas Asian and European subjects with the TLR2 2258A allele had an increased susceptibility to TB.ConclusionsThe meta-analysis indicated that TLR2 G2258A is associated with increased TB risk, especially in Asians and Europeans. TLR1 G1805T is associated with increased TB in Africans and American Hispanics. TLR6 C745T is associated with decreased TB risk. Our systematic review and meta-analysis reported an interesting preliminary conclusion, but this must be validated by future large-scale and functional studies in different populations.

A genome wide association study of pulmonary tuberculosis susceptibility in Indonesians

BackgroundThere is reason to expect strong genetic influences on the risk of developing active pulmonary tuberculosis (TB) among latently infected individuals. Many of the genome wide linkage and association studies (GWAS) to date have been conducted on African populations. In order to identify additional targets in genetically dissimilar populations, and to enhance our understanding of this disease, we performed a multi-stage GWAS in a Southeast Asian cohort from Indonesia.MethodsIn stage 1, we used the Affymetrix 100 K SNP GeneChip marker set to genotype 259 Indonesian samples. After quality control filtering, 108 cases and 115 controls were analyzed for association of 95,207 SNPs. In stage 2, we attempted validation of 2,453 SNPs with promising associations from the first stage, in 1,189 individuals from the same Indonesian cohort, and finally in stage 3 we selected 251 SNPs from this stage to test TB association in an independent Caucasian cohort (n = 3,760) from Russia.ResultsOur study suggests evidence of association (P = 0.0004-0.0067) for 8 independent loci (nominal significance P < 0.05), which are located within or near the following genes involved in immune signaling: JAG1, DYNLRB2, EBF1, TMEFF2, CCL17, HAUS6, PENK and TXNDC4.ConclusionsMechanisms of immune defense suggested by some of the identified genes exhibit biological plausibility and may suggest novel pathways involved in the host containment of infection with TB.

Genetic Variants in MARCO Are Associated with the Susceptibility to Pulmonary Tuberculosis in Chinese Han Population

BackgroundSusceptibility to tuberculosis is not only determined by Mycobacterium tuberculosis infection, but also by the genetic component of the host. Macrophage receptor with a collagenous structure (MARCO) is essential components required for toll like receptor-signaling in macrophage response to Mycobacterium tuberculosis, which may contribute to tuberculosis risk.Principal FindingsTo specifically investigated whether single nucleotide polymorphisms (SNPs) in MARCO gene are associated with pulmonary tuberculosis in Chinese Han population. By selecting tagging SNPs in MARCO gene, 17 tag SNPs were identified and genotyped in 923 pulmonary tuberculosis patients and 1033 healthy control subjects using a hospital based case-control association study. Single-point and haplotype analysis revealed an association in intron and exon region of MARCO gene. One SNP (rs17009726) was associated with susceptibility to pulmonary tuberculosis, where the carriers of the G allele had a 1.65 fold (95% CI = 1.32–2.05, p corrected = 9.27E–5) increased risk of pulmonary tuberculosis. Haplotype analysis revealed that haplotype GC containing G allele of 17009726 and haplotype TGCC (rs17795618T/A, rs1371562G/T, rs6761637T/C, rs2011839C/T) were also associated with susceptibility to pulmonary tuberculosis (p corrected = 0.0001 and 0.029, respectively).ConclusionsOur study suggested that genetic variants in MARCO gene were associated with pulmonary tuberculosis susceptibility in Chinese Han population, and the findings emphasize the importance of MARCO mediated immune responses in the pathogenesis of tuberculosis.

Association between gene polymorphisms of vitamin D receptor and pulmonary tuberculosis susceptibility: a meta-analysis

Background The vitamin D receptor ( VDR) gene is a primary candidate gene for tuberculosis susceptibility, but results of previous studies are somewhat contradictory and underpowered. Thus, it is essential to further explore the association between VDR gene polymorphisms and risk of pulmonary tuberculosis (PTB). Methods A systematic review and meta-analysis about the association between FokI, TaqI, ApaI and BsmI polymorphisms and PTB susceptibility was conducted. Statistical Package for Social Science (Version 13.0) and Review Manager (Version 4.2, The Cochrane Collaboration) were used to analyze the data reported in studies. Results A total of 13 studies with 2 262 cases and 2 833 controls were involved in the FokI polymorphism, and the results showed FokI polymorphism was associated with PTB susceptibility (allele f vs F: OR=1.12, 95% CI=[1.02, 1.23]; the additive effect model ff vs FF: OR=1.40, 95% CI=[1.10, 1.77]; the recessive genetic model ff vs Ff+FF: OR=1.39, 95% CI=[1.12, 1.71]). No significant associations were observed between TaqI (15 studies with 3 031 cases and 3 132 controls), ApaI (7 studies with 1 495 cases and 1 922 controls), BsmI (6 studies with 919 cases and 1 250 controls) variants and PTB susceptibility. Conclusion We found variant FokI polymorphism of VDR gene may play a risky role in PTB development, and the genetic model was presumed to be recessive.

Research on the association of DC-SIGN gene promoter polymorphisms with tuberculosis

Objective To study the relationship of two variants( -871A/G and -336A/G) polymorphisms of the DC-SIGN gene with the susceptibility to pulmonary tuberculosis in Chinese population.Methods Two hundred and thirty-seven tuberculosis cases and 244 controls were genotyped by pyrosequencing in this case-control study. The analysis of the relationship of the -871A/G and -336A/G polymorphisms with their susceptibility of pulmonary tuberculosis(PTB) and the relationship of the two variants with their clinical correlation of tuberculosis was performed by chi-square test. Results The genotypic frequencies of A/G + G/G and A/A of - 871, 37.6%, 62.4% respectively in cases, and 43.4%, 56. 6%respectively in controls, had no significant difference in statistics. And the genotypic frequencies of A/G + G/G and A/A of -336, 12. 2% ,87.8% respectively in cases, and 14.3% ,85.7% respectively in controls, had also no statistical difference between two groups. Interestingly, a significant association is disclosed between the promoter variant - 336G allele and fever in patients ( P = 0. 037, OR = 0. 191, 95 % CI:0. 040-0. 907 ). Conclusion The single nucleotide polymorphism of -871A/G and -336A/G in DCSIGN gene promoter might not be associated with the susceptibility to tuberculosis in Chinese. Tuberculosis patients with -336G allele are significantly protected fever. Key words: DC-SIGN gene; Tuberculosis; Polymorphism; Disease susceptibility

Human Toll-like receptor 4 polymorphismsTLR4Asp299Gly and Thr399Ile influence susceptibility and severity of pulmonary tuberculosis in the Asian Indian population

Genetic polymorphisms in Toll-like receptor 4, TLR4 896 A/G (Asp299Gly) and 1196 C/T (Thr399Ile) have been reported to influence TLR4 function and the innate host immune response to mycobacteria. We investigated the effect of these single nucleotide polymorphisms on susceptibility and severity of pulmonary tuberculosis (PTB) in the Asian Indian population. A significantly increased frequency of TLR4 Asp299Gly mutation was observed in the patient group (17%) as compared with healthy controls [8.8%, chi(2) = 10.7, P = 0.001,odds ratio (OR ) = 2.1]. On the other hand, the TLR4 Thr399Ile mutation occurred with comparable frequencies in the two groups (12.6% among patients and 9% in healthy controls). The PTB patients were categorized on the basis of their bacillary load as 3+, 2+, 1+, negative and on the extent of lung involvement as having minimal, moderate, and far-advanced lung disease. The 299Gly mutant occurred in homozygous state (GG) only in patients with high bacillary load (3+) and those with far-advanced lung disease. Similarly, the mutant 399Ile was significantly pronounced in these patients in the homozygous state (TT). The present data suggest that TLR4 substitutions at residues 299 and 399 are associated with pulmonary TB, particularly, the most severe disease.

NOS2A, TLR4, and IFNGR1 interactions influence pulmonary tuberculosis susceptibility in African-Americans.

Tuberculosis (TB) has substantial mortality worldwide with 5-10% of those exposed progressing to active TB disease. Studies in mice and humans indicate that the inducible nitric oxide synthase (iNOS) molecule plays an important role in immune response to TB. A mixed case-control association study of individuals with TB, relatives, or close contact controls was performed in 726 individuals (279 case and 166 control African-Americans; 198 case and 123 control Caucasians). Thirty-nine single nucleotide polymorphisms (SNPs) were selected from the NOS2A gene for single SNP, haplotype, and multilocus interaction analyses with other typed candidate genes using generalized estimating equations. In African-Americans, ten NOS2A SNPs were associated with TB. The strongest associations were observed at rs2274894 (odds ratio (OR) = 1.84, 95% confidence interval (CI) [1.23-2.77], p = 0.003) and rs7215373 (OR = 1.67, 95% CI [1.17-2.37], p = 0.004), both of which passed a false discovery rate correction for multiple comparisons (q* = 0.20). The strongest gene-gene interactions were observed between NOS2A rs2248814 and IFNGR1 rs1327474 (p = 0.0004) and NOS2A rs944722 and IFNGR1 rs1327474 (p = 0.0006). Three other SNPs in NOS2A interacted with TLR4 rs5030729 and five other NOS2A SNPs interacted with IFNGR1 rs1327474. No significant associations were observed in Caucasians. These results suggest that NOS2A variants may contribute to TB susceptibility, particularly in individuals of African descent, and may act synergistically with SNPs in TLR4 and IFNGR1.

Relationship between single nucleotide polymorphisms of NRAMP1 gene and susceptibility to pulmonary tuberculosis in workers exposed to silica dusts

To explore the relationship between polymorphisms of natural resistance-associated macrophage protein 1 (NRAMP1) gene and genetic susceptibility of pulmonary tuberculosis (PTB) in workers exposed to silica dusts. A 1:2 case control study of 61 male workers with PTB (50 silicosis patients and 11 unsilicosis workers) as the case group and 122 male PTB-free workers (100 silicosis patients and 22 unsilicosis workers) as the control group was conducted with the frequency matched for age of +/- 5 years, the job, the silica exposure, and the condition of cigarette smoking and alcohol drinking. The polymerase chain reaction-restrained fragment length polymorphism technique (PCR-RFLP) was used to detect the single nucleotide polymorphisms (SNPs) of NRAMP1 INT4 and D543N. There was a 2.73 times (95% CI: 1.32 approximately 5.64) increased risk of silicosis for individuals with C allele of NRAMP1 INT4 compared with individuals carrying homozygote (G/G), while SNPs of NRAMP1 D543N was not associated with PTB (P > 0.05). The G > C mutation of intron 4 of NRAMP1 gene might be a susceptible factor of silica for the workers exposed to PTB.

The decline of high drug resistance rate of pulmonary Mycobacterium tuberculosis isolates from a southern Taiwan medical centre, 1996–2000

To investigate the anti-tuberculosis drug resistance pattern of pulmonary tuberculosis isolates in southern Taiwan, we performed a hospital-based surveillance at a southern Taiwan medical centre from 1996 to 2000. The combined drug resistance rates to at least one of four first-line agents (isoniazid, rifampicin, ethambutol, streptomycin) was 52.4%, and to both isoniazid and rifampicin was 11.4%, indicating high resistance rates compared with those reported in the World Health Organization (WHO)/International Union Against Tuberculosis and Lung Disease (IUATLD) global project and in northern Taiwan. The resistance rates to two second-line drugs, cycloserine, and kanamycin, were 75.7 and 23.7%, respectively. A significant decreasing trend in resistance rates to all tested drugs except streptomycin was observed during the 5-year period. The resistance rates in 1996 and 2000 were 43.1 and 16.4% for isoniazid, 23.4 and 9.5% for rifampicin, 23.4 and 12.1% for ethambutol, 92.7 and 50.9% for pyrazinamide. The combined drug resistance rate may not be the most accurate tool as it includes previously treated cases that may inflate the resistance rate and cases without a history of treatment. However, the observation of trends in the susceptibility of pulmonary tuberculosis with the increasing percentages of tuberculosis patients receiving the complete treatment course and the decreasing percentages of cases lost to follow-up in Kaohsiung after the institution of new governmental regulations for case management in 1997, suggest that such intervention programs are useful.