Human Molecular Genetics Advance Access originally published online on October 20, 2008
Human Molecular Genetics 2009 18(2):381-388; doi:10.1093/hmg/ddn352
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MCP-1 promoter variant –362C associated with protection from pulmonary tuberculosis in Ghana, West Africa
1 Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany, 2 Institute of Medical Biometry and Statistics, University Hospital Schleswig-Holstein, Campus Lübeck, Lübeck, Germany, 3 Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory, Department of Medical Genetics, Cambridge Institute for Medical Research 4 Department of Medicine, University of Cambridge, Cambridge, UK 5 Department of Community Health, School of Medical Sciences, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana 6 Health Research Unit, Ministry of Health, Accra, Ghana 7 Kumasi Centre for Collaborative Research in Tropical Medicine, Kumasi, Ghana
* To whom correspondence should be addressed at: Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Bernhard Nocht Str. 74, 20359 Hamburg, Germany. Tel: +49 4042818501; Fax: +49 4042818512; Email: c.g.meyer{at}bni.uni-hamburg.de
Received July 8, 2008; Accepted October 17, 2008
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 (Pcorr) = 0.0012] and nuclear families (OR 0.72, Pcorr = 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, Pcorr = 0.00017) and in the affected families (OR 0.7, Pcorr = 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.