Ontology highlight
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.
SUBMITTER: Sabri A
PROVIDER: S-EPMC4111910 | biostudies-literature | 2014 Aug
REPOSITORIES: biostudies-literature
Sabri Ayoub A Grant Audrey V AV Cosker Kristel K El Azbaoui Safa S Abid Ahmed A Abderrahmani Rhorfi Ismail I Souhi Hicham H Janah Hicham H Alaoui-Tahiri Kebir K Gharbaoui Yasser Y Benkirane Majid M Orlova Marianna M Boland Anne A Deswarte Caroline C Migaud Melanie M Bustamante Jacinta J Schurr Erwin E Boisson-Dupuis Stephanie S Casanova Jean-Laurent JL Abel Laurent L El Baghdadi Jamila J
The Journal of infectious diseases 20140308 4
<h4>Background</h4>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.<h4>Methods</h4>We conducted a ...[more]