title: Variant G57E of mannose binding lectin associated with protection against tuberculosis caused by Mycobacterium africanum but not by M. tuberculosis.
abstract: Structural variants of the Mannose Binding Lectin (MBL) cause quantitative and qualitative functional deficiencies, which are associated with various patterns of susceptibility to infectious diseases and other disorders. We determined genetic MBL variants in 2010 Ghanaian patients with pulmonary tuberculosis (TB) and 2346 controls and characterized the mycobacterial isolates of the patients. Assuming a recessive mode of inheritance, we found a protective association between TB and the MBL2 G57E variant (odds ratio 0.60, confidence interval 0.4-0.9, P 0.008) and the corresponding LYQC haplotype (P(corrected) 0.007) which applied, however, only to TB caused by M. africanum but not to TB caused by M. tuberculosis. In vitro, M. africanum isolates bound recombinant human MBL more efficiently than did isolates of M. tuberculosis. We conclude that MBL binding may facilitate the uptake of M. africanum by macrophages, thereby promoting infection and that selection by TB may have favoured the spread of functional MBL deficiencies in regions endemic for M. africanum.
authors.affiliation: Department of Molecular Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Thye
authors.forename: Stefan
authors.initials: S
authors.lastname: Niemann
authors.forename: Kerstin
authors.initials: K
authors.lastname: Walter
authors.forename: Susanne
authors.initials: S
authors.lastname: Homolka
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Intemann
authors.forename: Margaret Amanua
authors.initials: MA
authors.lastname: Chinbuah
authors.forename: Anthony
authors.initials: A
authors.lastname: Enimil
authors.forename: John
authors.initials: J
authors.lastname: Gyapong
authors.forename: Ivy
authors.initials: I
authors.lastname: Osei
authors.forename: Ellis
authors.initials: E
authors.lastname: Owusu-Dabo
authors.forename: Sabine
authors.initials: S
authors.lastname: Rüsch-Gerdes
authors.forename: Rolf D
authors.initials: RD
authors.lastname: Horstmann
authors.forename: Stefan
authors.initials: S
authors.lastname: Ehlers
authors.forename: Christian G
authors.initials: CG
authors.lastname: Meyer
mesh_terms: D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006678:HIV / Q000472:pathogenicity; D006801:Humans; D037601:Mannose-Binding Lectin / Q000235:genetics* / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D020641:Polymorphism, Single Nucleotide; D013045:Species Specificity; D014397:Tuberculosis, Pulmonary / Q000235:genetics* / Q000382:microbiology / Q000821:virology
chemical_list: D037601:Mannose-Binding Lectin