Association study of genes controlling IL-12-dependent IFN-γ immunity: STAT4 alleles increase risk of pulmonary tuberculosis in Morocco.
J Infect Dis
; 210(4): 611-8, 2014 Aug 15.
Article
em En
| MEDLINE
| ID: mdl-24610875
ABSTRACT
BACKGROUND:
Only a minority of individuals infected with Mycobacterium tuberculosis develop clinical tuberculosis. Genetic epidemiological evidence suggests that pulmonary tuberculosis has a strong human genetic component. Previous genetic findings in Mendelian predisposition to more severe mycobacterial infections, including by M. tuberculosis, underlined the importance of the interleukin 12 (IL-12)/interferon γ (IFN-γ) circuit in antimycobacterial immunity.METHODS:
We conducted an association study in Morocco between pulmonary tuberculosis and a panel of single-nucleotide polymorphisms (SNPs) covering 14 core IL-12/IFN-γ circuit genes. The analyses were performed in a discovery family-based sample followed by replication in a case-control population.RESULTS:
Out of 228 SNPs tested in the family-based sample, 6 STAT4 SNPs were associated with pulmonary tuberculosis (P = .0013-.01). We replicated the same direction of association for 1 cluster of 3 SNPs encompassing the promoter region of STAT4. In the combined sample, the association was stronger among younger subjects (pulmonary tuberculosis onset <25 years) with an odds ratio of developing pulmonary tuberculosis at rs897200 for GG vs AG/AA subjects of 1.47 (1.06-2.04). Previous functional experiments showed that the G allele of rs897200 was associated with lower STAT4 expression.CONCLUSIONS:
Our present findings in a Moroccan population support an association of pulmonary tuberculosis with STAT4 promoter-region polymorphisms that may impact STAT4 expression.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tuberculose Pulmonar
/
Interferon gama
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Interleucina-12
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Predisposição Genética para Doença
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Fator de Transcrição STAT4
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Limite:
Adolescent
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Adult
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Aged
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Child
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Child, preschool
/
Female
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Humans
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Infant
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Male
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Middle aged
País/Região como assunto:
Africa
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Marrocos