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Association between TLR4 and TLR9 gene polymorphisms with development of pulmonary tuberculosis in Zahedan, southeastern Iran.

ABSTRACT: Some evidence suggests that a variety of genetic factors contribute to development of the tuberculosis (TB). TLR4 and TLR9 have been proposed as susceptibility genes for TB. This study was performed in 124 newly diagnosed TB cases and 149 healthy controls in a TB-endemic region of Iran. The TLR4 genes Asp299Gly, Thr399Ile, and TLR9 gene T-1486C polymorphisms were amplified by polymerase chain reaction (PCR) and then detected by PCR-restriction fragment length polymorphism (RFLP). The frequencies of the mutant alleles of TLR4 Arg299Gly, Thr399Ile, and TLR9 T-1486C polymorphisms were 0.8 versus 0.1, 5.6 versus 3, and 28.6 versus 25.2 in patients and controls, respectively, that were not significant. The synergic effect of TI,II/CC genotypes for TLR4 Thr399Ile and TLR9 T-1486C polymorphisms showed increased risk of PTB susceptibility. In conclusion, no significant relation was found between TLR4 and TLR9 polymorphisms alone and PTB. However, synergic effects of TLR4 Thr399Ile and TLR9-1486T/C polymorphisms might increase risk of PTB.

SUBMITTER: Jahantigh D

PROVIDER: S-EPMC3677666 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Association between TLR4 and TLR9 gene polymorphisms with development of pulmonary tuberculosis in Zahedan, southeastern Iran.

Jahantigh Danial D Salimi Saeedeh S Alavi-Naini Roya R Emamdadi Abolfazl A Owaysee Osquee Hamid H Farajian Mashhadi Farzaneh F

TheScientificWorldJournal 20130526

Some evidence suggests that a variety of genetic factors contribute to development of the tuberculosis (TB). TLR4 and TLR9 have been proposed as susceptibility genes for TB. This study was performed in 124 newly diagnosed TB cases and 149 healthy controls in a TB-endemic region of Iran. The TLR4 genes Asp299Gly, Thr399Ile, and TLR9 gene T-1486C polymorphisms were amplified by polymerase chain reaction (PCR) and then detected by PCR-restriction fragment length polymorphism (RFLP). The frequencies ...[more]

PMID: 23766695

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Project description:ObjectiveChronic obstructive pulmonary disease (COPD) and pulmonary tuberculosis (PTB) share a number of common risk factors, including innate immunity-related genetic factors. In the present study, we compared the role of genetic variations of the TLR4 gene in susceptibility to COPD and PTB and illuminated the underlying molecular mechanism of functional single-nucleotide polymorphisms (SNPs).MethodsA population-based case control study was performed in a Chinese Han population and included 152 COPD cases, 1601 PTB cases and 1727 controls. Five SNPs in the TLR4 gene (rs10759932, rs2737190, rs7873784, rs11536889, and rs10983755) were genotyped using TaqMan allelic discrimination technology. We estimated the effects of SNPs using the odds ratio (OR) together with 95% confidence interval (CI). Dual-luciferase reporter vectors expressing different genotypes of SNPs were constructed and transfected into the human HEK 293 T cell line to explore their effects on potential transcription activity.ResultsAfter Bonferroni correction, the genetic polymorphisms of all five SNPs remained significantly associated with COPD, while rs10759932 and rs2737190 were also associated with PTB. Compared with rs10759932-TT, individuals carrying TC (OR: 0.42, 95% CI: 0.28-0.64) or CC (OR: 0.24, 95% CI: 0.09-0.63) had a significantly reduced risk of COPD. However, individuals carrying TC (OR: 1.28, 95% CI: 1.11-1.49) or CC (OR: 1.26, 95% CI: 0.98-1.62) had an increased risk of PTB. The OR (95% CI) for allele rs10759932-C was 0.45 (0.32-0.62) for COPD and 1.18 (1.07-1.32) for PTB. For rs2737190, heterozygous AG was related to a decreased risk of COPD (OR: 0.32, 95% CI: 0.21-0.49) and an increased risk of PTB (OR: 1.30, 95% CI: 1.11-1.52). The dual-luciferase reporter assay showed decreased transcription activity caused by rs10759932-C and rs2737190-G.ConclusionGenetic polymorphisms of rs10759932 and rs2737190 in TLR4 are significantly related to both COPD and PTB but with inverse effects. The altered transcription activity caused by mutations in these two loci may partly explain the observed relationship.

Dataset Information

Association between TLR4 and TLR9 gene polymorphisms with development of pulmonary tuberculosis in Zahedan, southeastern Iran.

Publications

Association between TLR4 and TLR9 gene polymorphisms with development of pulmonary tuberculosis in Zahedan, southeastern Iran.

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