Distribution of insertion- and deletion-associated genetic polymorphisms among four Mycobacterium tuberculosis phospholipase C genes and associations with extrathoracic tuberculosis

A population-based study

Ying Kong, M. D. Cave, D. Yang, L. Zhang, C. F. Marrs, B. Foxman, J. H. Bates, F. Wilson, L. N. Mukasa, Z. H. Yang

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

The Mycobacterium tuberculosis genome contains four phospholipase C (PLC)-encoding genes, designated plcA, plcB, plcC, and plcD, respectively. Each of the four genes contributes to the overall PLC activity of M. tuberculosis. PLC is hypothesized to contribute to M. tuberculosis virulence. Infection of M. tuberculosis strains carrying a truncated plcD gene is associated with the occurrence of extrathoracic tuberculosis. However, whether the other three plc genes are also associated with extrathoracic tuberculosis remains to be assessed. We investigated the insertion- and deletion-associated genetic diversity in all four plc genes among 682 epidemiologically and clinically well-characterized M. tuberculosis clinical isolates using PCR, DNA sequencing, and Southern hybridization. Two hundred sixty-six (39%) of the 682 isolates had an interruption in at least one of the four plc genes, most often associated with an IS6110 insertion. The plcD gene interruption was the most common: it was observed in 233 (34%) of the isolates, compared to 4.7%, 4.1%, and 5.9% for plcA, plcB, and plcC gene interruption, respectively. The association between the plc gene genotypes and disease presentation was adjusted for clustering using generalized estimating equations for both bivariate and multivariate analyses. After controlling for the genotypes of the plcABC genes and the host-related risk factors, interruption in the plcD gene remained significantly associated with extrathoracic tuberculosis (odds ratio, 3.27; 95% confidence interval, 1.32 to 8.14). The data suggest that the plcD gene might play a more important role in the pathogenesis of thoracic TB than it does in the pathogenesis of extrathoracic TB.

Original languageEnglish (US)
Pages (from-to)6048-6053
Number of pages6
JournalJournal of Clinical Microbiology
Volume43
Issue number12
DOIs
StatePublished - Dec 1 2005

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Type C Phospholipases
Genetic Polymorphisms
Mycobacterium tuberculosis
Tuberculosis
Population
Genes
Genotype
DNA Sequence Analysis
Cluster Analysis
Virulence
Thorax
Multivariate Analysis
Odds Ratio
Genome
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)

Cite this

Distribution of insertion- and deletion-associated genetic polymorphisms among four Mycobacterium tuberculosis phospholipase C genes and associations with extrathoracic tuberculosis : A population-based study. / Kong, Ying; Cave, M. D.; Yang, D.; Zhang, L.; Marrs, C. F.; Foxman, B.; Bates, J. H.; Wilson, F.; Mukasa, L. N.; Yang, Z. H.

In: Journal of Clinical Microbiology, Vol. 43, No. 12, 01.12.2005, p. 6048-6053.

Research output: Contribution to journalArticle

Kong, Ying ; Cave, M. D. ; Yang, D. ; Zhang, L. ; Marrs, C. F. ; Foxman, B. ; Bates, J. H. ; Wilson, F. ; Mukasa, L. N. ; Yang, Z. H. / Distribution of insertion- and deletion-associated genetic polymorphisms among four Mycobacterium tuberculosis phospholipase C genes and associations with extrathoracic tuberculosis : A population-based study. In: Journal of Clinical Microbiology. 2005 ; Vol. 43, No. 12. pp. 6048-6053.
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abstract = "The Mycobacterium tuberculosis genome contains four phospholipase C (PLC)-encoding genes, designated plcA, plcB, plcC, and plcD, respectively. Each of the four genes contributes to the overall PLC activity of M. tuberculosis. PLC is hypothesized to contribute to M. tuberculosis virulence. Infection of M. tuberculosis strains carrying a truncated plcD gene is associated with the occurrence of extrathoracic tuberculosis. However, whether the other three plc genes are also associated with extrathoracic tuberculosis remains to be assessed. We investigated the insertion- and deletion-associated genetic diversity in all four plc genes among 682 epidemiologically and clinically well-characterized M. tuberculosis clinical isolates using PCR, DNA sequencing, and Southern hybridization. Two hundred sixty-six (39{\%}) of the 682 isolates had an interruption in at least one of the four plc genes, most often associated with an IS6110 insertion. The plcD gene interruption was the most common: it was observed in 233 (34{\%}) of the isolates, compared to 4.7{\%}, 4.1{\%}, and 5.9{\%} for plcA, plcB, and plcC gene interruption, respectively. The association between the plc gene genotypes and disease presentation was adjusted for clustering using generalized estimating equations for both bivariate and multivariate analyses. After controlling for the genotypes of the plcABC genes and the host-related risk factors, interruption in the plcD gene remained significantly associated with extrathoracic tuberculosis (odds ratio, 3.27; 95{\%} confidence interval, 1.32 to 8.14). The data suggest that the plcD gene might play a more important role in the pathogenesis of thoracic TB than it does in the pathogenesis of extrathoracic TB.",
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AB - The Mycobacterium tuberculosis genome contains four phospholipase C (PLC)-encoding genes, designated plcA, plcB, plcC, and plcD, respectively. Each of the four genes contributes to the overall PLC activity of M. tuberculosis. PLC is hypothesized to contribute to M. tuberculosis virulence. Infection of M. tuberculosis strains carrying a truncated plcD gene is associated with the occurrence of extrathoracic tuberculosis. However, whether the other three plc genes are also associated with extrathoracic tuberculosis remains to be assessed. We investigated the insertion- and deletion-associated genetic diversity in all four plc genes among 682 epidemiologically and clinically well-characterized M. tuberculosis clinical isolates using PCR, DNA sequencing, and Southern hybridization. Two hundred sixty-six (39%) of the 682 isolates had an interruption in at least one of the four plc genes, most often associated with an IS6110 insertion. The plcD gene interruption was the most common: it was observed in 233 (34%) of the isolates, compared to 4.7%, 4.1%, and 5.9% for plcA, plcB, and plcC gene interruption, respectively. The association between the plc gene genotypes and disease presentation was adjusted for clustering using generalized estimating equations for both bivariate and multivariate analyses. After controlling for the genotypes of the plcABC genes and the host-related risk factors, interruption in the plcD gene remained significantly associated with extrathoracic tuberculosis (odds ratio, 3.27; 95% confidence interval, 1.32 to 8.14). The data suggest that the plcD gene might play a more important role in the pathogenesis of thoracic TB than it does in the pathogenesis of extrathoracic TB.

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