Microarray analysis of gene expression associated with extrapulmonary dissemination of tuberculosis.
OBJECTIVE
Although extrapulmonary organs are involved in 20% of patients with tuberculosis, the host genetic factors associated with the extrapulmonary dissemination of tuberculosis are not yet known. The aim of this study was to identify the host genetic factors associated with the extrapulmonary dissemination of tuberculosis by comparing gene expression profiles of patients who had recovered from extrapulmonary tuberculosis and those who had recovered from pulmonary tuberculosis.


METHODS
Five patients from each group were enrolled. Total RNA was extracted from peripheral blood mononuclear cells that had been incubated for 48 h with whole lysate of Mycobacterium tuberculosis (H37Rv, 0.5 microg/mL). Gene expression profiles were acquired using the GeneChip array and its applied systems. Gene expression profiles from five patients with previous extrapulmonary tuberculosis and one pooled control sample from five patients with previous pulmonary tuberculosis were analysed and compared. Genes that were expressed concordantly in more than 80% of arrays and that showed more than twofold changes in at least one array among samples from patients who had recovered from extrapulmonary tuberculosis were identified.


RESULTS
Compared with the control sample, the expression of 16 genes, including those for tumour necrosis factor (TNF)-alpha and cathepsin W, was increased, and the expression of 45 genes including that for TNF-receptor superfamily member 7 (TNFRSF7), was decreased in the extrapulmonary tuberculosis patients. The altered expression of the TNF-alpha, cathepsin W and TNFRSF7 genes was confirmed by quantitative RT-PCR.


CONCLUSIONS
Altered expression of the genes for TNF-alpha, cathepsin W and TNFRSF7 may be risk factors for the extrapulmonary dissemination of tuberculosis in humans.
Kim
Deog Kyeom
DK
Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University College of Medicine, 28 Yongon-Dong, Chongno-Gu, Seoul 110-744, Korea.
Park
Geun Min
GM
Hwang
Yong Il
YI
Kim
Hyun Ji
HJ
Han
Sung Koo
SK
Shim
Young-Soo
YS
Yim
Jae-Joon
JJ
D000328:Adult; D000368:Aged; D056664:Cathepsin W; D002403:Cathepsins / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014376:Tuberculosis / Q000235:genetics* / Q000473:pathology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; D002403:Cathepsins; C534187:CTSW protein, human; D056664:Cathepsin W; D003546:Cysteine Endopeptidases