title: TNF -308G>A single nucleotide polymorphism is associated with leprosy among Brazilians: a genetic epidemiology assessment, meta-analysis, and functional study.
abstract: Leprosy is an infectious disease caused by Mycobacterium leprae. Tumor necrosis factor (TNF) plays a key role in the host response. Some association studies have implicated the single nucleotide polymorphism TNF -308G>A in leprosy susceptibility, but these results are still controversial. We first conducted 4 association studies (2639 individuals) that showed a protective effect of the -308A allele (odds ratio [OR] = 0.77; P = .005). Next, results of a meta-analysis reinforced this association after inclusion of our new data (OR = 0.74; P = .04). Furthermore, a subgroup analysis including only Brazilian studies suggested that the association is specific to this population (OR = 0.63; P = .005). Finally, functional analyses using whole blood cultures showed that patients carrying the -308A allele produced higher TNF levels after lipopolysaccharide (LPS) (6 hours) and M. leprae (3 hours) stimulation. These results reinforce the association between TNF and leprosy and suggest the -308A allele as a marker of disease resistance, especially among Brazilians.
authors.affiliation: Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (FIOCRUZ), Rio de Janeiro, Brazil.
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Cardoso
authors.forename: Ana Carla
authors.initials: AC
authors.lastname: Pereira
authors.forename: Vânia N
authors.initials: VN
authors.lastname: Brito-de-Souza
authors.forename: Sandra M B
authors.initials: SM
authors.lastname: Duraes
authors.forename: Marcelo
authors.initials: M
authors.lastname: Ribeiro-Alves
authors.forename: José Augusto C
authors.initials: JA
authors.lastname: Nery
authors.forename: Ângela S
authors.initials: ÂS
authors.lastname: Francio
authors.forename: Patrícia R
authors.initials: PR
authors.lastname: Vanderborght
authors.forename: Francisco P C
authors.initials: FP
authors.lastname: Parelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Alter
authors.forename: Jorge Luís
authors.initials: JL
authors.lastname: Salgado
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Sampaio
authors.forename: Adalberto R
authors.initials: AR
authors.lastname: Santos
authors.forename: Maria Leide W R
authors.initials: ML
authors.lastname: Oliveira
authors.forename: Euzenir N
authors.initials: EN
authors.lastname: Sarno
authors.forename: Erwin
authors.initials: E
authors.lastname: Schurr
authors.forename: Marcelo T
authors.initials: MT
authors.lastname: Mira
authors.forename: Antonio G
authors.initials: AG
authors.lastname: Pacheco
authors.forename: Milton O
authors.initials: MO
authors.lastname: Moraes
mesh_terms: D000328:Adult; D001938:Brazil / Q000453:epidemiology; D016022:Case-Control Studies; D004247:DNA / Q000737:chemistry / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007918:Leprosy / Q000453:epidemiology / Q000235:genetics* / Q000382:microbiology; D008297:Male; D009166:Mycobacterium leprae / Q000302:isolation & purification*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult
chemical_list: D014409:Tumor Necrosis Factor-alpha; D004247:DNA