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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

The overlap of study subjects between the current study (n = 1974) and the previous genome-wide association study (GWAS, n = 1139) [29].
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pone-0041618-g001: The overlap of study subjects between the current study (n = 1974) and the previous genome-wide association study (GWAS, n = 1139) [29].

Mentions: Previously polymorphisms in various genes were genotyped on a two-stage genome-wide association study (GWAS) using Illumina’s GoldenGate Assay according to manufacturer instructions, aiming to discover genes relevant in pulmonary TB susceptibility in the same Indonesian cohort involved in the current study [29]. Among the SNPs studied, five were in autophagy genes and were included in our data analysis (Table 1). The overlap of study subjects between the current study and the GWAS is shown in Figure 1.


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)

The overlap of study subjects between the current study (n = 1974) and the previous genome-wide association study (GWAS, n = 1139) [29].
© Copyright Policy
Related In: Results  -  Collection

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

pone-0041618-g001: The overlap of study subjects between the current study (n = 1974) and the previous genome-wide association study (GWAS, n = 1139) [29].
Mentions: Previously polymorphisms in various genes were genotyped on a two-stage genome-wide association study (GWAS) using Illumina’s GoldenGate Assay according to manufacturer instructions, aiming to discover genes relevant in pulmonary TB susceptibility in the same Indonesian cohort involved in the current study [29]. Among the SNPs studied, five were in autophagy genes and were included in our data analysis (Table 1). The overlap of study subjects between the current study and the GWAS is shown in Figure 1.

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