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

Thorsten Thye, 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

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)381-8
Number of pages8
JournalHuman Molecular Genetics
Volume18
Issue number2
DOIs
Publication statusPublished - 15 Jan 2009

Cite this

Thye, Thorsten ; Nejentsev, Sergey ; Intemann, Christopher D ; Browne, Edmund N ; Chinbuah, Margaret Amanua ; Gyapong, John ; Osei, Ivy ; Owusu-Dabo, Ellis ; Zeitels, Lauren R ; Herb, Florian ; Horstmann, Rolf D ; Meyer, Christian G. / MCP-1 promoter variant -362C associated with protection from pulmonary tuberculosis in Ghana, West Africa. In: Human Molecular Genetics. 2009 ; Vol. 18, No. 2. pp. 381-8.
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title = "MCP-1 promoter variant -362C associated with protection from pulmonary tuberculosis in Ghana, West Africa",
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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author = "Thorsten Thye and Sergey Nejentsev and Intemann, {Christopher D} and Browne, {Edmund N} and Chinbuah, {Margaret Amanua} and John Gyapong and Ivy Osei and Ellis Owusu-Dabo and Zeitels, {Lauren R} and Florian Herb and Horstmann, {Rolf D} and Meyer, {Christian G}",
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Thye, T, Nejentsev, S, Intemann, CD, Browne, EN, Chinbuah, MA, Gyapong, J, Osei, I, Owusu-Dabo, E, Zeitels, LR, Herb, F, Horstmann, RD & Meyer, CG 2009, 'MCP-1 promoter variant -362C associated with protection from pulmonary tuberculosis in Ghana, West Africa' Human Molecular Genetics, vol. 18, no. 2, pp. 381-8. https://doi.org/10.1093/hmg/ddn352

MCP-1 promoter variant -362C associated with protection from pulmonary tuberculosis in Ghana, West Africa. / Thye, Thorsten; Nejentsev, Sergey; Intemann, Christopher D; Browne, Edmund N; Chinbuah, Margaret Amanua; Gyapong, John; Osei, Ivy; Owusu-Dabo, Ellis; Zeitels, Lauren R; Herb, Florian; Horstmann, Rolf D; Meyer, Christian G.

In: Human Molecular Genetics, Vol. 18, No. 2, 15.01.2009, p. 381-8.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - MCP-1 promoter variant -362C associated with protection from pulmonary tuberculosis in Ghana, West Africa

AU - Thye, Thorsten

AU - Nejentsev, Sergey

AU - Intemann, Christopher D

AU - Browne, Edmund N

AU - Chinbuah, Margaret Amanua

AU - Gyapong, John

AU - Osei, Ivy

AU - Owusu-Dabo, Ellis

AU - Zeitels, Lauren R

AU - Herb, Florian

AU - Horstmann, Rolf D

AU - Meyer, Christian G

PY - 2009/1/15

Y1 - 2009/1/15

N2 - 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.

AB - 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.

KW - Adult

KW - Case-Control Studies

KW - Chemokine CCL2/genetics

KW - Female

KW - Genetic Predisposition to Disease

KW - Ghana/epidemiology

KW - Humans

KW - Male

KW - Polymorphism, Genetic

KW - Promoter Regions, Genetic

KW - Russia/epidemiology

KW - Tuberculosis, Pulmonary/epidemiology

U2 - 10.1093/hmg/ddn352

DO - 10.1093/hmg/ddn352

M3 - Article

VL - 18

SP - 381

EP - 388

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 2

ER -