MCP-1 promoter variant 2362C associated with protection from pulmonary tuberculosis in Ghana, West Africa
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Date
2008
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Publisher
Oxford University Press
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 mono cytechemoattractant 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 22581 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 22581G was significantly associated with resistance to TB in cases versus controls [odds ratio (OR) 0.81, corrected P-value (Pcorr) 5 0.0012] and nuclear families (OR 0.72, Pcorr 5 0.04) and not with disease susceptibility, whereas in the Russian sample no evidence of association was found (P 50.86). Our and other results do not support an association of MCP-1 22581 with TB. In the Ghanaian population, eight additional MCP-1 polymorphisms were genotyped. MCP-1 2362C was associated with resistance to TB in the case–control collection (OR 0.83, Pcorr 5 0.00017) and in the affected families (OR 0.7, Pcorr 50.004). Linkage disequilibrium (LD) and logistic regression analyses indicate that, in Ghanaians, the effect results exclusively from the MCP-1 2362 variant, whereas the effect of 22581 may in part be explained by its LD with 2362.
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Keywords
Tuberculosis
Citation
Human Molecular Genetics, 2009, Vol. 18, No. 2