<i>TLR1</i> polymorphisms are significantly associated with the occurrence, presentation and drug-adverse reactions of tuberculosis in Western Chinese adults

Peng, Wu; Chen, Hao; Zhao, Zhenzhen; Hu, Xuejiao; Zhou, Yi; Li, Yingyu; Yang, Liang; Wang, Xuemei; Song, Jiajia; Liu, Tangyuheng; Wu, Qian; Bai, Hao; Lu, Xiaojun; Chen, Jie

doi:10.18632/oncotarget.23067

Cited by 10 publications

(9 citation statements)

References 41 publications

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“…rs5743557, located 595 bp upstream of the TLR1 gene, might influence the promoter activity of this gene. rs5743557_A was reported to be significantly associated with decreased TB risk in Chinese Tibetans, while this relationship was only observed in Chinese Han women and no significant association was seen in Chinese Han children (20,25,26). After meta-analysis in our paper, rs5743557_A showed a relationship with decreased TB susceptibility in the Chinese adult population.…”

Section: Discussionmentioning

confidence: 46%

“…These reports contained of four studies, two of Chinese Han adults, one of Chinese Tibetan adults and one of Chinese Han children (Table S1). As demonstrated in Figure 1 (20,25,26), there was high degree of heterogeneity among the included studies (P<0.001 and I 2 =85.9%). After stratifying by age, no significant heterogeneity was observed (P=0.102), and rs5743557_A was associated with reduced TB risk and the odds ratio was 0.80 in the Chinese adult group (P<0.001, 95% CI: 0.72-0.88).…”

Section: Meta-analysis Results Of Relationship Between Rs5743557 and mentioning

confidence: 94%

“…As shown in the flow diagram ( Figure S1), only three reports including 2,179 TB patients and 2,049 healthy controls were enrolled (20,25,26). These reports contained of four studies, two of Chinese Han adults, one of Chinese Tibetan adults and one of Chinese Han children (Table S1).…”

Section: Meta-analysis Results Of Relationship Between Rs5743557 and mentioning

confidence: 99%

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Association of the TLR1 variant rs5743557 with susceptibility to tuberculosis

Zhang¹,

Wang²,

Wang³

et al. 2019

J. Thorac. Dis

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Background: Toll-like receptor 1 (TLR1) and TLR6 play important roles in the innate immune response against Mycobacterium tuberculosis (M.TB) via interactions with TIR domain-containing adaptor protein (TIRAP) and myeloid differentiation primary response 88 (MYD88). The aim of this study was to investigate the relationship of TLR1, TLR6, MYD88 and TIRAP polymorphisms with susceptibility to latent tuberculosis infection (LTBI) and tuberculosis (TB). Methods: In total, 204 uninfected healthy controls (HC), 201 individuals with LTBI and 209 TB patients were enrolled. Two interferon-γ release assays were used to differentiate individuals with LTBI from uninfected controls. TagSNPs of the four genes were genotyped by the SNPscan TM Kit. The Haploview 4.2 and SHEsis software packages were combined to perform linkage disequilibrium (LD) and haplotype analyses. Multifactor dimensionality reduction (MDR) software was used to investigate genegene interaction. The Stata 12.0 software was used to perform meta-analysis of the relationship between rs5743557 and TB susceptibility. Results: The AA genotype of rs5743557 was associated with reduced TB risk (P=0.006) and the AA/GA genotypes of TLR1 rs5743604 were associated with increased TB risk (P=0.017) when the LTBI group was compared with the TB group. The frequency of TLR1 haplotype rs4833095-rs5743604 CG was significantly higher in the LTBI group than in the TB group (P=0.019877). However, only the relationship between rs5743557 and TB susceptibility remained significant after 1000-fold permutation testing (P=0.023). The meta-analysis suggested that rs5743557_A was associated with decreased TB risk in the Chinese adult population (P<0.001, OR 0.80, 95% CI: 0.72-0.88). No significant gene-gene interactions were found. Conclusions: The results of our study suggest that the tagSNP rs5743557 of TLR1 is associated with the risk of TB.

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Section: Discussionmentioning

confidence: 46%

Section: Meta-analysis Results Of Relationship Between Rs5743557 and mentioning

confidence: 94%

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Association of the TLR1 variant rs5743557 with susceptibility to tuberculosis

Zhang¹,

Wang²,

Wang³

et al. 2019

J. Thorac. Dis

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“…While rs76600635 was recently associated with thrombocytopenia in Western Chinese patients undergoing treatment for tuberculosis, to the best of our knowledge no other clinical associations have been reported [34]. In a prior study, when a TLR1 construct with the rs76600635 variant was transfected into HEK cells and stimulated with Pam 3 CSK 4 , a TLR1 agonist, no change in NF-κB activation was observed [35].…”

Section: Discussionmentioning

confidence: 99%

Exonic sequencing identifies TLR1 genetic variation associated with mortality in Thais with melioidosis

Wright

Emond

Lovelace-Macon

et al. 2019

Emerging Microbes & Infections

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Melioidosis, an infectious disease caused by the bacterium Burkholderia pseudomallei , is a common cause of sepsis in Southeast Asia. We investigated whether novel TLR1 coding variants are associated with outcome in Thai patients with melioidosis. We performed exonic sequencing on a discovery set of patients with extreme phenotypes (mild vs. severe) of bacteremic melioidosis. We analysed the association of missense variants in TLR1 with severe melioidosis in a by-gene analysis. We then genotyped key variants and tested the association with death in two additional sets of melioidosis patients. Using a by-gene analysis, TLR1 was associated with severe bacteremic melioidosis ( P = 0.016). One of the eight TLR1 variants identified, rs76600635, a common variant in East Asians, was associated with in-hospital mortality in a replication set of melioidosis patients (adjusted odds ratio 1.71, 95% CI 1.01–2.88, P = 0.04.) In a validation set of patients, the point estimate of effect of the association of rs76600635 with 28-day mortality was similar but not statistically significant (adjusted odds ratio 1.81, 95% CI 0.96–3.44, P = 0.07). Restricting the validation set analysis to patients recruited in a comparable fashion to the discovery and replication sets, rs76600635 was significantly associated with 28-day mortality (adjusted odds ratio 3.88, 95% CI 1.43–10.56, P = 0.01). Exonic sequencing identifies TLR1 as a gene associated with a severe phenotype of bacteremic melioidosis. The TLR1 variant rs76600635, common in East Asian populations, may be associated with poor outcomes from melioidosis. This variant has not been previously associated with outcomes in sepsis and requires further study.

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“…The SNPscan assay was a rapid multiplex genetic screening system, and its basic principle was to recognize SNP alleles by using the high specificity of ligase binding reactions ( 21 ). The specific process of SNPscan genotyping was mentioned in previous study ( 22 ). The sample could be included in the final analysis, only when all SNPs were successfully genotyped in this sample.…”

Section: Methodsmentioning

confidence: 99%

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

Zhang

Li²,

Wang³

et al. 2022

Front. Immunol.

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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.

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TLR1 polymorphisms are significantly associated with the occurrence, presentation and drug-adverse reactions of tuberculosis in Western Chinese adults

Cited by 10 publications

References 41 publications

Association of the TLR1 variant rs5743557 with susceptibility to tuberculosis

Association of the TLR1 variant rs5743557 with susceptibility to tuberculosis

Exonic sequencing identifies TLR1 genetic variation associated with mortality in Thais with melioidosis

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

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