title: Wound healing genes and susceptibility to cutaneous leishmaniasis in Brazil: role of COL1A1.
abstract: Previous studies have demonstrated a role for wound healing genes in resolution of cutaneous lesions caused by Leishmania spp. in both mice and humans, including the gene FLI1 encoding Friend leukemia virus integration 1. Reduction of Fli1 expression in mice has been shown to result in up-regulation of collagen type I alpha 1 (Col1a1) and alpha 2 (Col1a2) genes and, conversely, in down-regulation of the matrix metalloproteinase 1 (Mmp1) gene, suggesting that Fli1 suppression is involved in activation of the profibrotic gene program. Here we examined single nucleotide polymorphisms (SNPs) in these genes as risk factors for cutaneous (CL) and mucosal leishmaniasis (ML), and leishmaniasis per se, caused by L. braziliensis in humans. SNPs were genotyped in 168 nuclear families (250 CL; 87 ML cases) and replicated in 157 families (402 CL; 39 ML cases). Family-based association tests (FBAT) showed the strongest association between SNPs rs1061237 (combined P=0.002) and rs2586488 (combined P=0.027) at COL1A1 and CL disease. This contributes to our further understanding of the role of wound healing in the resolution of CL disease, providing potential for therapies modulating COL1A1 via drugs acting on FLI1.
authors.affiliation: National Institute of Science and Technology in Tropical Diseases, Brazil and Federal University of Bahia, Salvador, Brazil. Electronic address: lucasfedrigo@hotmail.com.
authors.forename: Lucas
authors.initials: L
authors.lastname: Almeida
authors.affiliation: National Institute of Science and Technology in Tropical Diseases, Brazil and Federal University of Bahia, Salvador, Brazil. Electronic address: joycemouraoliveira@yahoo.com.br.
authors.forename: Joyce
authors.initials: J
authors.lastname: Oliveira
authors.affiliation: National Institute of Science and Technology in Tropical Diseases, Brazil and Federal University of Bahia, Salvador, Brazil. Electronic address: luizhenriquesg@yahoo.com.br.
authors.forename: Luiz Henrique
authors.initials: LH
authors.lastname: Guimarães
authors.affiliation: National Institute of Science and Technology in Tropical Diseases, Brazil and Federal University of Bahia, Salvador, Brazil. Electronic address: edgar@ufba.br.
authors.forename: Edgar M
authors.initials: EM
authors.lastname: Carvalho
authors.affiliation: Telethon Kids Institute, The University of Western Australia, Subiaco, Western Australia, Australia; Cambridge Institute for Medical Research and Department of Medicine, University of Cambridge School of Clinical Medicine, Cambridge, UK. Electronic address: jmb37@cam.ac.uk.
authors.forename: Jenefer M
authors.initials: JM
authors.lastname: Blackwell
authors.affiliation: National Institute of Science and Technology in Tropical Diseases, Brazil and Federal University of Bahia, Salvador, Brazil. Electronic address: leacastel@hotmail.com.
authors.forename: Léa
authors.initials: L
authors.lastname: Castellucci
mesh_terms: D000328:Adult; D001938:Brazil; D015331:Cohort Studies; D024042:Collagen Type I / Q000235:genetics*; D000090602:Collagen Type I, alpha 1 Chain; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D016773:Leishmaniasis, Cutaneous / Q000235:genetics*; D007897:Leishmaniasis, Mucocutaneous / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D014945:Wound Healing / Q000235:genetics*; D055815:Young Adult
chemical_list: C000716127:COL1A1 protein, human; C000601279:COL1A2 protein, human; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: COL1A1; Cutaneous leishmaniasis; Gene analysis; Wound healing