Abstract
Chemokines play a major role in leukocyte recruitment during the formation of tuberculous granulomas. We studied the association between genetic polymorphisms of three chemokines, monocyte chemoattractant protein-1 (MCP-1), RANTES (regulated on activation, normal T cell expressed and secreted) and macrophage inflammatory protein-1α (MIP-1α), and tuberculosis (TB). The distribution of five functionally significant single-nucleotide polymorphisms (SNPs), MCP-1 −2518A/G, RANTES −403G/A, −28C/G and In1.1T/C as well as MIP-1α +459C/T was not found to be different between patients with TB and healthy control subjects of the Hong Kong Chinese population. However, differences in linkage disequilibrium (LD) of the SNPs of RANTES and in distribution of the haplotypes of RANTES between patients with TB and healthy controls (P<0.0001) were found. Two risk haplotypes of RANTES, A-C-T and G-C-C, at positions −403, −28 and In1.1, respectively, were identified. Furthermore, combining the genotypes of RANTES −403 and In1.1, two diplotypes GA/TT (P<0.001) and GG/TC (P<0.0001) showed strong association with TB. Our findings support the association between RANTES functional polymorphisms and TB.
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Acknowledgements
We thank Ms Ivy Ng for sequencing primer designs and technical support. The present study was approved by the Ethics Committees of the Faculty of Medicine, The University of Hong Kong and the Department of Health, Hong Kong Special Administrative Region (HKSAR), China. All authors do not have any commercial or other association that might pose a conflict of the interest in this research. This study was supported by research grants to AKSC (HKU CRCG#10205036 and 10205662). SFC was supported by Research Postgraduate Studentship of The University of Hong Kong. Part of the information in this paper was presented at the 3rd Hong Kong Medical Genetics Conference in April 2005 in Hong Kong Special Administrate Region, China and at the European Human Genetics Conference 2005 in May 2005 in Prague, Czech Republic. Information in this paper formed part of the MPhil thesis of SFC at The University of Hong Kong.
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Chu, SF., Tam, C., Wong, H. et al. Association between RANTES functional polymorphisms and tuberculosis in Hong Kong Chinese. Genes Immun 8, 475–479 (2007). https://doi.org/10.1038/sj.gene.6364412
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DOI: https://doi.org/10.1038/sj.gene.6364412
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