title: FLI1 polymorphism affects susceptibility to cutaneous leishmaniasis in Brazil.
abstract: Mapping murine genes controlling cutaneous leishmaniasis (CL) identified Fli1 as a candidate influencing resistance to L. major and enhanced wound healing. We examine FLI1 as a gene controlling CL and mucosal leishmaniasis (ML) caused by L. braziliensis in humans. Intron 1 single nucleotide polymorphisms tagging promoter and enhancer elements were analysed in 168 nuclear families (250 CL; 87 ML cases) and replicated in 157 families (402 CL; 39 ML cases). Robust case-pseudocontrol logistic regression analysis showed association between allele C (odds ratio (OR) 1.65; 95% confidence interval 1.18-2.29; P=0.003) of FLI1_rs7930515 and CL in the primary sample that was confirmed (OR 1.60; 95% confidence interval 1.10-2.33; P=0.014) in the replication set (combined P=1.8 × 10(-4)). FLI1_rs7930515 is in linkage disequilibrium with the functional GAn microsatellite in the proximal promoter. Haplotype associations extended across the enhancer, which was not polymorphic. ML associated with inverse haplotypes compared with CL. Wound healing is therefore important in CL, providing potential for therapies modulating FLI1.
authors.affiliation: Serviço de Imunologia, Hospital Universitário Professor Edgard Santos, Federal University of Bahia, Salvador, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Castellucci
authors.forename: S E
authors.initials: SE
authors.lastname: Jamieson
authors.forename: E N
authors.initials: EN
authors.lastname: Miller
authors.forename: L F
authors.initials: LF
authors.lastname: de Almeida
authors.forename: J
authors.initials: J
authors.lastname: Oliveira
authors.forename: A
authors.initials: A
authors.lastname: Magalhães
authors.forename: L H
authors.initials: LH
authors.lastname: Guimarães
authors.forename: M
authors.initials: M
authors.lastname: Lessa
authors.forename: E
authors.initials: E
authors.lastname: Lago
authors.forename: A R
authors.initials: AR
authors.lastname: de Jesus
authors.forename: E M
authors.initials: EM
authors.lastname: Carvalho
authors.forename: J M
authors.initials: JM
authors.lastname: Blackwell
mesh_terms: D000483:Alleles; D001938:Brazil; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007438:Introns; D016773:Leishmaniasis, Cutaneous / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051789:Proto-Oncogene Protein c-fli-1 / Q000235:genetics*; D044469:Racial Groups / Q000235:genetics
chemical_list: C078433:FLI1 protein, human; D051789:Proto-Oncogene Protein c-fli-1