TY - JOUR
KW - Adult
KW - Brazil
KW - Case-Control Studies
KW - DNA
KW - Female
KW - Genetic Variation
KW - genotype
KW - Humans
KW - leprosy
KW - Male
KW - Mycobacterium leprae
KW - polymerase chain reaction
KW - Polymorphism, Single Nucleotide
KW - Tumor Necrosis Factor-alpha
KW - Young Adult
AU - Cardoso C
AU - Pereira AC
AU - Brito-de-Souza V
AU - Duraes S
AU - Ribeiro-Alves M
AU - Nery JA
AU - Francio Â
AU - Vanderborght P
AU - Parelli FP C
AU - Alter A
AU - Salgado JL
AU - Sampaio E
AU - Santos AR
AU - Oliveira MLWD
AU - Sarno E
AU - Schurr E
AU - Mira MT
AU - Pacheco A
AU - Moraes M
AB - <p>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.</p>
BT - The Journal of infectious diseases
C1 - http://www.ncbi.nlm.nih.gov/pubmed/21917899?dopt=Abstract
C2 - UK
CY - Oxford
DA - 2011 Oct 15
DO - 10.1093/infdis/jir521
IS - 8
J2 - J. Infect. Dis.
LA - eng
N2 - <p>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.</p>
PB - Oxford University Press
PP - Oxford
PY - 2011
SP - 1256
EP - 63
T2 - The Journal of infectious diseases
TI - TNF -308G>A single nucleotide polymorphism is associated with leprosy among Brazilians: a genetic epidemiology assessment, meta-analysis, and functional study.
VL - 204
SN - 1537-6613
ER -