title: Host genetic factors in American cutaneous leishmaniasis: a critical appraisal of studies conducted in an endemic area of Brazil.
abstract: American cutaneous leishmaniasis (ACL) is a vector-transmitted infectious disease with an estimated 1.5 million new cases per year. In Brazil, ACL represents a significant public health problem, with approximately 30,000 new reported cases annually, representing an incidence of 18.5 cases per 100,000 inhabitants. Corte de Pedra is in a region endemic for ACL in the state of Bahia (BA), northeastern Brazil, with 500-1,300 patients treated annually. Over the last decade, population and family-based candidate gene studies were conducted in Corte de Pedra, founded on previous knowledge from studies on mice and humans. Notwithstanding limitations related to sample size and power, these studies contribute important genetic biomarkers that identify novel pathways of disease pathogenesis and possible new therapeutic targets. The present paper is a narrative review about ACL immunogenetics in BA, highlighting in particular the interacting roles of the wound healing gene FLI1 with interleukin-6 and genes SMAD2 and SMAD3 of the transforming growth factor beta signalling pathway. This research highlights the need for well-powered genetic and functional studies on Leishmania braziliensis infection as essential to define and validate the role of host genes in determining resistance/susceptibility regarding this disease.
authors.affiliation: Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, Universidade Federal da Bahia, Salvador, BA, Brasil.
authors.forename: Léa Cristina
authors.initials: LC
authors.lastname: Castellucci
authors.affiliation: Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, Universidade Federal da Bahia, Salvador, BA, Brasil.
authors.forename: Lucas Frederico de
authors.initials: LF
authors.lastname: Almeida
authors.affiliation: Telethon Kids Institute, The University of Western Australi, Perth, Australia.
authors.forename: Sarra Elisabeth
authors.initials: SE
authors.lastname: Jamieson
authors.affiliation: Telethon Kids Institute, The University of Western Australi, Perth, Australia.
authors.forename: Michaela
authors.initials: M
authors.lastname: Fakiola
authors.affiliation: Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais, Universidade Federal da Bahia, Salvador, BA, Brasil.
authors.forename: Edgar Marcelino de
authors.initials: EM
authors.lastname: Carvalho
authors.affiliation: Telethon Kids Institute, The University of Western Australi, Perth, Australia.
authors.forename: Jenefer Mary
authors.initials: JM
authors.lastname: Blackwell
mesh_terms: D000818:Animals; D001938:Brazil / Q000453:epidemiology; D019353:Endemic Diseases; D005819:Genetic Markers / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D016773:Leishmaniasis, Cutaneous / Q000453:epidemiology / Q000235:genetics*; D051379:Mice
chemical_list: D005819:Genetic Markers