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Polymorphisms in autophagy genes and susceptibility to tuberculosis.

Songane M, Kleinnijenhuis J, Alisjahbana B, Sahiratmadja E, Parwati I, Oosting M, Plantinga TS, Joosten LA, Netea MG, Ottenhoff TH, van de Vosse E, van Crevel R - PLoS ONE (2012)

Bottom Line: The same autophagy polymorphisms were studied in correlation with ex-vivo production of TNF, IL-1β, IL-6, IL-8, IFN-γ and IL-17 in healthy volunteers.No association was found between TB and polymorphisms in the genes ATG10, ATG16L2, ATG2B, ATG5, ATG9B, IRGM, LAMP1, LAMP3, P2RX7, WIPI1, MTOR and ATG4C.All associations found lost statistical significance after correction for multiple testing.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

ABSTRACT
Recent data suggest that autophagy is important for intracellular killing of Mycobacterium tuberculosis, and polymorphisms in the autophagy gene IRGM have been linked with susceptibility to tuberculosis (TB) among African-Americans, and with TB caused by particular M. tuberculosis genotypes in Ghana. We compared 22 polymorphisms of 14 autophagy genes between 1022 Indonesian TB patients and 952 matched controls, and between patients infected with different M. tuberculosis genotypes, as determined by spoligotyping. The same autophagy polymorphisms were studied in correlation with ex-vivo production of TNF, IL-1β, IL-6, IL-8, IFN-γ and IL-17 in healthy volunteers. No association was found between TB and polymorphisms in the genes ATG10, ATG16L2, ATG2B, ATG5, ATG9B, IRGM, LAMP1, LAMP3, P2RX7, WIPI1, MTOR and ATG4C. Associations were found between polymorphisms in LAMP1 (p = 0.02) and MTOR (p = 0.02) and infection with the successful M. tuberculosis Beijing genotype. The polymorphisms examined were not associated with M. tuberculosis induced cytokines, except for a polymorphism in ATG10, which was linked with IL-8 production (p = 0.04). All associations found lost statistical significance after correction for multiple testing. This first examination of a broad set of polymorphisms in autophagy genes fails to show a clear association with TB, with M. tuberculosis Beijing genotype infection or with ex-vivo pro-inflammatory cytokine production.

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Related in: MedlinePlus

Scatter plots of TNF, IFN-γ, and IL-17 produced after stimulation of PBMC with M. tuberculosis stratified for genotypes of both investigated polymorphisms in IRGM.
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pone-0041618-g002: Scatter plots of TNF, IFN-γ, and IL-17 produced after stimulation of PBMC with M. tuberculosis stratified for genotypes of both investigated polymorphisms in IRGM.

Mentions: Association between host genotype and M. tuberculosis induced cytokine production by PBMC was examined in healthy Caucasian individuals. Table 5 shows the difference in M. tuberculosis induced production of TNF, IL-1β, IL-6, IL-8, IFN-γ and IL-17 by PBMC isolated from individuals stratified for different genotype of autophagy related genes. Six of these polymorphisms showed no polymorphic distribution in the Caucasian individuals and could therefore not be analysed. With the exception of ATG10 (rs1864183), for which a significant difference was found in IL-8 production between individuals with an AA and GG genotype (p = 0.04), no associations were observed between the investigated cytokines and the autophagy related polymorphisms. Figure 2 presents scatter plots of TNF, IFN-γ, and IL-17 stratified for genotypes of both investigated polymorphisms in IRGM which was previously linked with susceptibility to TB.


Polymorphisms in autophagy genes and susceptibility to tuberculosis.

Songane M, Kleinnijenhuis J, Alisjahbana B, Sahiratmadja E, Parwati I, Oosting M, Plantinga TS, Joosten LA, Netea MG, Ottenhoff TH, van de Vosse E, van Crevel R - PLoS ONE (2012)

Scatter plots of TNF, IFN-γ, and IL-17 produced after stimulation of PBMC with M. tuberculosis stratified for genotypes of both investigated polymorphisms in IRGM.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3412843&req=5

pone-0041618-g002: Scatter plots of TNF, IFN-γ, and IL-17 produced after stimulation of PBMC with M. tuberculosis stratified for genotypes of both investigated polymorphisms in IRGM.
Mentions: Association between host genotype and M. tuberculosis induced cytokine production by PBMC was examined in healthy Caucasian individuals. Table 5 shows the difference in M. tuberculosis induced production of TNF, IL-1β, IL-6, IL-8, IFN-γ and IL-17 by PBMC isolated from individuals stratified for different genotype of autophagy related genes. Six of these polymorphisms showed no polymorphic distribution in the Caucasian individuals and could therefore not be analysed. With the exception of ATG10 (rs1864183), for which a significant difference was found in IL-8 production between individuals with an AA and GG genotype (p = 0.04), no associations were observed between the investigated cytokines and the autophagy related polymorphisms. Figure 2 presents scatter plots of TNF, IFN-γ, and IL-17 stratified for genotypes of both investigated polymorphisms in IRGM which was previously linked with susceptibility to TB.

Bottom Line: The same autophagy polymorphisms were studied in correlation with ex-vivo production of TNF, IL-1β, IL-6, IL-8, IFN-γ and IL-17 in healthy volunteers.No association was found between TB and polymorphisms in the genes ATG10, ATG16L2, ATG2B, ATG5, ATG9B, IRGM, LAMP1, LAMP3, P2RX7, WIPI1, MTOR and ATG4C.All associations found lost statistical significance after correction for multiple testing.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.

ABSTRACT
Recent data suggest that autophagy is important for intracellular killing of Mycobacterium tuberculosis, and polymorphisms in the autophagy gene IRGM have been linked with susceptibility to tuberculosis (TB) among African-Americans, and with TB caused by particular M. tuberculosis genotypes in Ghana. We compared 22 polymorphisms of 14 autophagy genes between 1022 Indonesian TB patients and 952 matched controls, and between patients infected with different M. tuberculosis genotypes, as determined by spoligotyping. The same autophagy polymorphisms were studied in correlation with ex-vivo production of TNF, IL-1β, IL-6, IL-8, IFN-γ and IL-17 in healthy volunteers. No association was found between TB and polymorphisms in the genes ATG10, ATG16L2, ATG2B, ATG5, ATG9B, IRGM, LAMP1, LAMP3, P2RX7, WIPI1, MTOR and ATG4C. Associations were found between polymorphisms in LAMP1 (p = 0.02) and MTOR (p = 0.02) and infection with the successful M. tuberculosis Beijing genotype. The polymorphisms examined were not associated with M. tuberculosis induced cytokines, except for a polymorphism in ATG10, which was linked with IL-8 production (p = 0.04). All associations found lost statistical significance after correction for multiple testing. This first examination of a broad set of polymorphisms in autophagy genes fails to show a clear association with TB, with M. tuberculosis Beijing genotype infection or with ex-vivo pro-inflammatory cytokine production.

Show MeSH
Related in: MedlinePlus