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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
ALOX5 variants associated with susceptibility to human pulmonary tuberculosis
Human Molecular Genetics, Volume 17, No. 7, Year 2008
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Description
The 5-lipoxygenase (ALOX5)-derived lipid mediators leukotrienes and lipoxins have regulatory functions in inflammation by modulating activities of immune cells and cytokine production. Recently, it was shown in ALOX5-/- mice that host control of Mycobacterium tuberculosis is regulated by 5-lipoxygenase (5-LO). ALOX5 polymorphisms were genotyped in 1916 sputum-positive patients with pulmonary tuberculosis (TB) from Ghana and in 2269 exposed, apparently healthy controls. Polymorphisms of a variable number of tandem repeats (VNTR) of the ALOX5 promoter and of the exonic non-synonymous variant g.760G>A were analysed by fragment length determination and fluorescence resonance energy transfer, respectively, and DNA sequencing. Mycobacterial lineages of >1400 isolates were differentiated biochemically and genetically. Carriers of one variant (n repeats # 5) and one wild-type VNTR allele (n = 5) or of the exonic allele g.760A had a higher risk of TB [Pcorrected = 0.026, odds ratio (OR) 1.19 (95% CI 1.04-1.37) and P corrected = 0.026, OR 1.21 (95% CI 1.04-1.41), respectively]. The association of the exonic variant was stronger in infections caused by the mycobacterial lineage M. africanum West-African 2 [Pcorrected = 0.024, OR 1.70; (95% CI 1.2-2.6)]. Determination of haplotypes revealed the strongest associaton with TB for the 'non-5/760A' haplotype compared with the 'non-5/760G' haplotype (P = 0.003, OR 1.50). Our observation of an association of ALOX5 variants with susceptibility to TB contributes evidence of the importance of 5-LO products to the regulation of immune responses to M. tuberculosis. © The Author 2008. Published by Oxford University Press. All rights reserved.
Authors & Co-Authors
Herb, Florian
Unknown Affiliation
Thye, Thorsten
Unknown Affiliation
Niemann, Stefan
Unknown Affiliation
Browne, Edmund Nii Laryea
Unknown Affiliation
Chinbuah, Margaret Amanua
Unknown Affiliation
Gyapong, John O.
Unknown Affiliation
Osei, Ivy Frances
Unknown Affiliation
Owusu-Dabo, Ellis
Unknown Affiliation
Werz, Oliver
Unknown Affiliation
Rüsch-Gerdes, Sabine
Unknown Affiliation
Horstmann, Rolf Dieter
Unknown Affiliation
Meyer, Christian G.
Unknown Affiliation
Statistics
Citations: 96
Authors: 12
Affiliations: 8
Identifiers
Doi:
10.1093/hmg/ddm378
ISSN:
09646906
e-ISSN:
14602083
Research Areas
Genetics And Genomics
Infectious Diseases
Study Design
Case-Control Study
Study Locations
Ghana