MCP-1 promoter variant -362C associated with protection from pulmonary tuberculosis in Ghana, West Africa - PubMed (original) (raw)

. 2009 Jan 15;18(2):381-8.

doi: 10.1093/hmg/ddn352. Epub 2008 Oct 20.

Sergey Nejentsev, Christopher D Intemann, Edmund N Browne, Margaret Amanua Chinbuah, John Gyapong, Ivy Osei, Ellis Owusu-Dabo, Lauren R Zeitels, Florian Herb, Rolf D Horstmann, Christian G Meyer

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MCP-1 promoter variant -362C associated with protection from pulmonary tuberculosis in Ghana, West Africa

Thorsten Thye et al. Hum Mol Genet. 2009.

Abstract

Current endeavour focuses on human genetic factors that contribute to susceptibility to or protection from tuberculosis (TB). Monocytes are crucial in containing Mycobacterium tuberculosis infection, and the monocyte chemoattractant protein-1 (MCP-1) cytokine plays a role in their recruitment to the site of infection. The G allele of the MCP-1 promoter polymorphism at position -2581 relative to the ATG transcription start codon has been described to be associated in Mexican and Korean TB patients with increased susceptibility to TB. We genotyped this and additional MCP-1 variants in sample collections comprising more than 2000 cases with pulmonary TB and more than 2300 healthy controls and 332 affected nuclear families from Ghana, West Africa, and more than 1400 TB patients and more than 1500 controls from Russia. In striking contrast to previous reports, MCP-1 -2581G was significantly associated with resistance to TB in cases versus controls [odds ratio (OR) 0.81, corrected P-value (P(corr)) = 0.0012] and nuclear families (OR 0.72, P(corr) = 0.04) and not with disease susceptibility, whereas in the Russian sample no evidence of association was found (P = 0.86). Our and other results do not support an association of MCP-1 -2581 with TB. In the Ghanaian population, eight additional MCP-1 polymorphisms were genotyped. MCP-1 -362C was associated with resistance to TB in the case-control collection (OR 0.83, P(corr) = 0.00017) and in the affected families (OR 0.7, P(corr) = 0.004). Linkage disequilibrium (LD) and logistic regression analyses indicate that, in Ghanaians, the effect results exclusively from the MCP-1 -362 variant, whereas the effect of -2581 may in part be explained by its LD with -362.

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Figures

Figure 1.

Figure 1.

Pairwise LD (_r_2) plots of MCP-1 variants of the Ghanaian study group (GHN) (A), a Mexican population from California (MXL) (B), a population of the US residents of northern and western European ancestry (CEU) (C), the Yoruba population from Nigeria (YRI) (D). MXL, CEU and YRI data are extracted from the HapMap database. Nucleotide positions of rs numbers are given in Table 6. LDs compared between the different populations consisted of the same allelic combinations.

Figure 2.

Figure 2.

Meta-analysis of five case–control studies analysing the allelic association between the MCP-1 variant 2581A>G and susceptibility to TB. Black squares represent the ORs of each study/ethnicity. The pooled OR (P = 0.09) is indicated by the diamond.

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References

    1. Takiff H.E. Host genetics and susceptibility. In: Palomino J.C., Leão S.C., Ritacco V., editors. Tuberculosis 2007. From Basic Science to Patient Care. 2007. pp. 207–262. Available at www.tuberculosistextbook.com/
    1. Blackwell J.M., Black G.F., Peacock C.S., Miller E.N., Sibthorpe D., Gnananandha D., Shaw J.J., Silveira F., Lins-Lainson Z., Ramos F., et al. Immunogenetics of leishmanial and mycobacterial infections: the Belem Family Study. Philos. Trans. R. Soc. Lond. B. Biol. Sci. 1997;352:1331–1345. - PMC - PubMed
    1. Jamieson S.E., Miller E.N., Black G.F., Peacock C.S., Cordell H.J., Howson J.M., Shaw M.A., Burgner D., Xu W., Lins-Lainson Z., et al. Evidence for a cluster of genes on chromosome 17q11–q21 controlling susceptibility to tuberculosis and leprosy in Brazilians. Genes Immun. 2004;5:46–57. - PubMed
    1. Flores-Villanueva P.O., Ruiz-Morales J.A., Song C.H., Flores L.M., Jo E.K., Montaño M., Barnes P.F., Selman M., Granados J. A functional promoter polymorphism in monocyte chemoattractant protein-1 is associated with increased susceptibility to pulmonary tuberculosis. J. Exp. Med. 2005;202:1649–1658. - PMC - PubMed
    1. Chu S.F., Tam C.M., Wong H.S., Kam K.M., Lau Y.L., Chiang A.K. Association between RANTES functional polymorphisms and tuberculosis in Hong Kong Chinese. Genes Immun. 2007;8:475–479. - PubMed

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