Đang chuẩn bị nút TẢI XUỐNG, xin hãy chờ
Tải xuống
The monocyte chemoattractant protein 1 (MCP-1) is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis (TB) case-control study group, associations of the MCP1 -362C and the MCP1 -2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico, Korea, Peru and Zambia. This inconsistency prompted us to further investigate the MCP1 gene in order to determine causal variants or haplotypes genetically and functionally | Intemann et al. BMC Genetics 2011 12 34 http www.biomedcentral.com 1471-2156 12 34 BMC Genetics RESEARCH ARTICLE Open Access MCP1 haplotypes associated with protection from pulmonary tuberculosis L VI r Z XK r 1 I nm 1 2 I M Z Xk r Fz I I ir 1 2 D I v-r t CzA rrtnr 1 E I I I r i A I ir i I L z 3 4 I z-s. L t k .z i z i5 Christopher D Intemann Thorsten Thye Birgit Forster Ellis Owusu-Dabo John Gyapong Rolf D Horstmann1 and Christian G Meyer1 Abstract Background The monocyte chemoattractant protein 1 MCP-1 is involved in the recruitment of lymphocytes and monocytes and their migration to sites of injury and cellular immune reactions. In a Ghanaian tuberculosis TB case-control study group associations of the MCP1 -362C and the MCP1 -2581G alleles with resistance to TB were recently described. The latter association was in contrast to genetic effects previously described in study groups originating from Mexico Korea Peru and Zambia. This inconsistency prompted us to further investigate the MCP1 gene in order to determine causal variants or haplotypes genetically and functionally. Results A 14 base-pair deletion in the first MCP1 intron int1del554-567 was strongly associated with protection against pulmonary TB OR 0.84 CI 0.77-0.92 Pcorrected 0.00098 . Compared to the wildtype combination a haplotype comprising the -2581G and -362C promoter variants and the intronic deletion conferred an even stronger protection than did the -362C variant alone OR 0.78 CI 0.69-0.87 Pnominai 0.00002 adjusted Pgiobai 0.0028 . In a luciferase reporter gene assay a significant reduction of luciferase gene expression was observed in the two constructs carrying the MCP1 mutations -2581 A or G plus the combination -362C and int1del554-567 compared to the wildtype haplotype P 0.02 and P 0.006 . The associated variants in particular the haplotypes composed of these latter variants result in decreased MCP-1 expression and a decreased risk of pulmonary TB. Conclusions In addition to the results of
