title: Association of a new FCN3 haplotype with high ficolin-3 levels in leprosy.
abstract: Leprosy is a chronic inflammatory disease caused by Mycobacterium leprae that mainly affects the skin and peripheral nervous system, leading to a high disability rate and social stigma. Previous studies have shown a contribution of genes encoding products of the lectin pathway of complement in the modulation of the susceptibility to leprosy; however, the ficolin-3/FCN3 gene impact on leprosy is currently unknown. The aim of the present study was to investigate if FCN3 polymorphisms (rs532781899: g.1637delC, rs28362807: g.3524_3532insTATTTGGCC and rs4494157: g.4473C>A) and ficolin-3 serum levels play a role in the susceptibility to leprosy. We genotyped up to 190 leprosy patients (being 114 (60%) lepromatous), and up to 245 controls with sequence-specific PCR. We also measured protein levels using ELISA in 61 leprosy and 73 controls. FCN3 polymorphisms were not associated with disease, but ficolin-3 levels were higher in patients with FCN3 *2B1 (CinsA) haplotype (p = 0.032). Median concentration of ficolin-3 was higher in leprosy per se (26034 ng/mL, p = 0.005) and lepromatous patients (28295 ng/mL, p = 0.016) than controls (18231 ng/mL). In addition, high ficolin-3 levels (>33362 ng/mL) were more common in leprosy per se (34.4%) and in lepromatous patients (35.5%) than controls (19.2%; p = 0.045 and p = 0.047, respectively). Our results lead us to suggest that polymorphisms in the FCN3 gene cooperate to increase ficolin-3 concentration and that it might contribute to leprosy susceptibility by favoring M. leprae infection.
authors.affiliation: Laboratory of Molecular Immunopathology, Department of Clinical Pathology, HC/UFPR, Curitiba, PR, Brazil.
authors.forename: Fabiana Antunes
authors.identifier: 0000-0003-4116-2324
authors.initials: FA
authors.lastname: Andrade
authors.affiliation: Laboratory of Molecular Immunopathology, Department of Clinical Pathology, HC/UFPR, Curitiba, PR, Brazil.
authors.forename: Marcia Holsbach
authors.initials: MH
authors.lastname: Beltrame
authors.affiliation: Laboratory of Human Molecular Genetics, Department of Genetics, UFPR, Curitiba, PR, Brazil.
authors.forename: Valéria Bumiller
authors.initials: VB
authors.lastname: Bini
authors.affiliation: Laboratory of Molecular Immunopathology, Department of Clinical Pathology, HC/UFPR, Curitiba, PR, Brazil.
authors.forename: Letícia Boslooper
authors.initials: LB
authors.lastname: Gonçalves
authors.affiliation: Laboratory of Molecular Immunopathology, Department of Clinical Pathology, HC/UFPR, Curitiba, PR, Brazil.|Laboratory of Human Molecular Genetics, Department of Genetics, UFPR, Curitiba, PR, Brazil.
authors.forename: Angelica Beate Winter
authors.initials: AB
authors.lastname: Boldt
authors.affiliation: Laboratory of Molecular Immunopathology, Department of Clinical Pathology, HC/UFPR, Curitiba, PR, Brazil.
authors.forename: Iara Jose
authors.initials: IJ
authors.lastname: de Messias-Reason
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D020022:Genetic Predisposition to Disease; D006023:Glycoproteins / Q000097:blood* / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D037102:Lectins / Q000097:blood* / Q000235:genetics*; D007918:Leprosy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D044967:Serum / Q000737:chemistry; D055815:Young Adult
chemical_list: C109662:FCN3 protein, human; D006023:Glycoproteins; D037102:Lectins