Variant G57E of mannose binding lectin associated with protection against tuberculosis caused by Mycobacterium africanum but not by M. tuberculosis

• Published in: PloS one 2011-06, Vol.6 (6), p.e20908-e20908
• Main Authors: Thye, Thorsten, Niemann, Stefan, Walter, Kerstin, Homolka, Susanne, Intemann, Christopher D, Chinbuah, Margaret Amanua, Enimil, Anthony, Gyapong, John, Osei, Ivy, Owusu-Dabo, Ellis, Rüsch-Gerdes, Sabine, Horstmann, Rolf D, Ehlers, Stefan, Meyer, Christian G
• Format: Article
• Language: English
• Subjects: Binding; Biology; Biometrics; Case-Control Studies; Collaboration; Communicable diseases; Confidence intervals; Disease susceptibility; DNA fingerprints; Drug resistance; Epidemiology; Genetic aspects; Genetic Predisposition to Disease - genetics; Genotype; Haplotypes; Health services; Hepatitis; Heredity; HIV; HIV - pathogenicity; Human immunodeficiency virus; Humans; Infectious diseases; Inflammation; Lectins; Macrophages; Mannose; Mannose-Binding Lectin - genetics; Mannose-Binding Lectin - metabolism; Medical research; Medicine; Monosaccharides; Mycobacterium; Mycobacterium tuberculosis; Mycobacterium tuberculosis - classification; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - pathogenicity; Pathogens; Patients; Polymorphism, Single Nucleotide; Population; Species Specificity; Tuberculosis; Tuberculosis, Pulmonary - genetics; Tuberculosis, Pulmonary - microbiology; Tuberculosis, Pulmonary - virology; White people; Whites
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0020908

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.