@article{23916,
  keywords = {Adolescent, Adult, African Continental Ancestry Group, Aged, Aged, 80 and over, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, genotype, Humans, Lectins, leprosy, Leprosy, lepromatous, Male, Middle Aged, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Young Adult},
  author = {Boldt A and Sanchez MIN and Stahlke E and Steffensen R and Thiel S and Jensenius J and Prevedello FC and Mira M and Kun JF J and Messias-Reason LJT},
  title = {Susceptibility to leprosy is associated with M-ficolin polymorphisms.},
  abstract = {<p><b>PURPOSE: </b>Mycobacterium leprae exploits complement activation and opsonophagocytosis to infect phagocytes. M-ficolin 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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>Ten haplotypes were identified with sequence-specific PCR and/or haplotype-specific sequencing. We found evidence for a protective codominant additive effect of FCN1*-542A-144C with leprosy in Euro-Brazilians (P=0.003, PBf =0.021, OR=0.243 [CI95% =0.083-0.71]), which was independent of age, ethnic group and gender effects (P=0.029). There was a trend for a positive association of the -399A variant in Afro-Brazilians (P=0.022, PBf =0.154, OR=4.151 [CI95% =1.115-15.454], as well as for a negative association of the FCN1*3A haplotype with lepromatous leprosy, compared with less severe forms of the disease (P=0.016, PBf =0.112, OR=0.324 [CI95% =0.123-0.858]). Danish individuals with this haplotype presented M-ficolin 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 (P=0.031).</p><p><b>CONCLUSIONS: </b>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.</p>},
  year = {2013},
  journal = {Journal of clinical immunology},
  volume = {33},
  pages = {210-9},
  month = {2013 Jan},
  issn = {1573-2592},
  doi = {10.1007/s10875-012-9770-4},
  language = {eng},
}