Susceptibility to Leprosy is Associated with M-ficolin Polymorphisms
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ORIGINAL RESEARCH
Susceptibility to Leprosy is Associated with M-ficolin Polymorphisms Angelica B. W. Boldt & Maria Iolanda N. Sanchez & Ewalda R. S. Stahlke & Rudi Steffensen & Steffen Thiel & Jens C. Jensenius & Flávia Costa Prevedello & Marcelo Távora Mira & Jürgen F. J. Kun & Iara J. T. Messias-Reason Received: 6 February 2012 / Accepted: 14 August 2012 / Published online: 1 September 2012 # Springer Science+Business Media, LLC 2012
Abstract Purpose Mycobacterium leprae exploits complement activation and opsonophagocytosis to infect phagocytes. Mficolin is encoded by the FCN1 gene and initiates the lectin pathway on monocyte surfaces. We investigated FCN1 promoter polymorphisms that could be responsible for the high interindividual variability of M-ficolin levels and for modulating leprosy susceptibility. Methods We genotyped rs2989727 (−1981 G > A), rs28909068 (−791 G > A), rs10120023 (−542 G > A), rs17039495 (−399 G > A), rs28909976 (−271IndelT), rs10117466 (−144C > A) and rs10858293 (+33 T > G) in 400 controls and 315 leprosy patients from Southern Brazil, and in 296 Danish healthy individuals with known M-ficolin levels. Results Ten haplotypes were identified with sequencespecific PCR and/or haplotype-specific sequencing. We found evidence for a protective codominant additive effect
of FCN1*−542A–144C with leprosy in Euro-Brazilians (P00.003, PBf00.021, OR00.243 [CI95%00.083–0.71]), which was independent of age, ethnic group and gender effects (P00.029). There was a trend for a positive association of the −399A variant in Afro-Brazilians (P00.022, PBf00.154, OR04.151 [CI95%01.115–15.454], as well as for a negative association of the FCN1*3A haplotype with lepromatous leprosy, compared with less severe forms of the disease (P00.016, PBf00.112, OR00.324 [CI95%00.123– 0.858]). Danish individuals with this haplotype presented Mficolin levels higher than the population average of circa 1,000 ng/ml, and −542A–144C, which is able to modify the recognition of transcription factors in silico, occurred in individuals with levels under the 25 percentil (P00.031). Conclusions Our data provide the first evidence that FCN1 polymorphisms are associated with leprosy. M-ficolin may represent a novel key to understand the immunopathogenesis of M. leprae infection.
In memorian (28.04.2011). We miss Prof. Jürgen F. J. Kun as a wonderful friend and excellent scientist. A. B. W. Boldt : M. I. N. Sanchez : I. J. T. Messias-Reason Laboratório de Imunopatologia Molecular – Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, Brazil E. R. S. Stahlke Departamento Estadual de Saúde do Paraná, Curitiba, Brazil R. Steffensen Department of Clinical Immunology, Aalborg Hospital, 9000 Aalborg, DK, Denmark S. Thiel : J. C. Jensenius Department of Medical Microbiology and Immunology, Aarhus University, Aarhus C 8000 DK, Denmark
F. C. Prevedello : M. T. Mira Núcleo de Investigação Molecular Avançada, Programa de Pós-Graduação em Ciências da Saúde, Pontifícia Universidade Católica do Paraná, Curitiba, Brazil J. F. J. Kun Institut
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