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J Infect Dis ; 201(9): 1422-35, 2010 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-20350193

RESUMO

BACKGROUND: Because of its wide spectrum of clinical manifestations and its well-defined immunological complications, leprosy is a useful disease for studying genetic regulation of the host response to infection. We hypothesized that polymorphisms in the nucleotide-binding oligomerization domain containing 2 (NOD2) gene, for a cytosolic receptor known to detect mycobacteria, are associated with susceptibility to leprosy and its clinical outcomes. METHODS: We used a case-control study design with 933 patients in Nepal. Our study included 240 patients with type 1 (reversal) reactions and 124 patients with type 2 (erythema nodosum leprosum) reactions. We compared the frequencies of 32 common polymorphisms in the NOD2 gene region between patients with the different clinical types of leprosy as well as between the patients and 101 control participants without leprosy. RESULTS: Four polymorphisms were associated with susceptibility to leprosy when comparing allele frequencies, and 8 were associated when comparing genotype frequencies with a dominant model. Five polymorphisms were associated with protection from reversal reaction in an allelic analysis, and 7 were associated with reversal reaction with a dominant model. Four polymorphisms were associated with increased susceptibility to erythema nodosum leprosum in an allelic analysis, whereas 7 of 32 polymorphisms were associated with a dominant model. CONCLUSION: These data suggest that NOD2 genetic variants are associated with susceptibility to leprosy and the development of leprosy reactive states.


Assuntos
Hanseníase/genética , Proteína Adaptadora de Sinalização NOD2/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Alelos , Estudos de Casos e Controles , Eritema Nodoso/genética , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Genótipo , Haplótipos/genética , Humanos , Hanseníase Virchowiana/genética , Masculino , Pessoa de Meia-Idade , Nepal , Proteína Adaptadora de Sinalização NOD2/fisiologia
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