The Association between Mannan-Binding Lectin Gene Polymorphism and Clinical Leprosy: New Insight into an Old Paradigm

• Published in: The Journal of infectious diseases Vol. 196; no. 9; pp. 1379 - 1385
• Main Authors: de Messias-Reason, Iara J., Boldt, Angélica B. W., Braga, Anna Carolina Moraes, Stahlke, Ewalda Von Rosen Seeling, Dornelles, Luciana, Pereira-Ferrari, Lilian, Kremsner, Peter G., Kun, Jürgen F. J.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 01.11.2007; University of Chicago Press
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Alleles; Bacteria; Bacterial diseases; Biological and medical sciences; Borderline leprosy; Case-Control Studies; Exons; Female; Genotype; Genotypes; Haplotypes; Human bacterial diseases; Humans; Infectious diseases; Lectins; Lepromatous leprosy; Leprosy; Leprosy - genetics; Male; Mannose-Binding Lectin - genetics; Medical sciences; Middle Aged; Mycobacterium leprae; Polymorphism, Genetic; Tropical bacterial diseases; Tuberculoid leprosy; Tuberculosis; Infection; Lectin; Skin disease; Gene; Bacteriosis; Leprosy; Mycobacterial infection; Polymorphism
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/521627

Background. Mannan-binding lectin (MBL), a soluble protein of innate immunity, is known to play a role in pathogen recognition and clearance. For more than a decade, it has been proposed that MBL deficiency may be protective against intracellular pathogens, such as Mycobacterium leprae. Methods. The polymorphisms at the promoter and exon 1 regions of the MBL2 gene were assessed by polymerase chain reaction and sequencing performed on 264 patients with leprosy and 214 matched healthy control subjects from southern Brazil. Results. The distribution of MBL2-gene polymorphisms in patients was significantly different from that in controls, with a decreased frequency of haplotypes/genotypes associated with low expression of circulating MBL in lepromatous patients when compared with tuberculoid patients (odds ratio [OR] for haplotypes, 0.56 [95% confidence interval {CI}, 0.33–0.93] [P=.020]; OR for genotypes, 0.31 [95% CI, 0.13–0.71] [P=.004]). The LYPA haplotype was associated with susceptibility to leprosy per se (OR, 2.25 [95% CI, 1.31–3.88] [P=.003]) and to progression to the lepromatous (OR, 2.2 [95% CI, 1.21–4.05] [P=.008]) and borderline (OR, 2.98 [95% CI, 1.29–6.87] [P=.008]) forms of the disease. Conclusions. These results suggest that MBL2-gene polymorphisms play a role in susceptibility to leprosy per se and in the clinical progression of the disease.