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The association between microsatellite polymorphisms in intron II of the human Toll-like receptor 2 gene and tuberculosis among Koreans

Genes & Immunity volume 7, pages 150–155 (2006)Cite this article

Abstract

The observation that Toll-like receptor (TLR)2-deficient mice are highly susceptible to mycobacteria suggests that mutations altering TLR2 expression may impair host response to Mycobacterium tuberculosis. We evaluated the association between guanine-thymine (GT) repeat polymorphism in intron II of the TLR2 gene and the presence of tuberculosis (TB) in Koreans. The numbers of GT repeats were determined by PCR and gene scans for 176 TB patients and 196 controls. The recombinant TLR2 promoter/exonI/exonII/intronII/luciferase constructs including three representative repeats: (GT)13, (GT)20, and (GT)24 were transfected into K562 cells, and luciferase activities were estimated and compared. The expression of TLR2 on CD14+ peripheral blood mononuclear cells (PBMC) from healthy volunteers were measured with flow cytometry. Genotypes with shorter GT repeats were more common among TB patients (49.4 vs 37.7%, P=0.02). This observation was confirmed among 82 other TB patients as a validation cohort. Shorter GT repeats were associated with weaker promoter activities and lower TLR2 expression on CD14+ PBMCs. In conclusion, the development of TB disease in Koreans was associated with shorter GT repeats in intron II of the TLR2 gene. This association is correlated with lower expression of TLR2 through weaker promoter activity for genes with shorter GT repeats.

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Acknowledgements

This work was supported by Grant (09-2003-005) from the SNUH Research Fund and in part through the Division of Intramural Research, NIH.

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Authors and Affiliations

  1. Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, and Lung Institute, Seoul National University College of Medicine, Chongno-Gu, Seoul, Republic of Korea

    J-J Yim, H W Lee, H S Lee, Y W Kim, S K Han & Y-S Shim

  2. Immunopathogenesis Section, Laboratory of Clinical Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    S M Holland

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Yim, JJ., Lee, H., Lee, H. et al. The association between microsatellite polymorphisms in intron II of the human Toll-like receptor 2 gene and tuberculosis among Koreans. Genes Immun 7, 150–155 (2006). https://doi.org/10.1038/sj.gene.6364274

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