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Journal of Clinical Microbiology, December 2005, p. 6048-6053, Vol. 43, No. 12
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.12.6048-6053.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Distribution of Insertion- and Deletion-Associated Genetic Polymorphisms among Four Mycobacterium tuberculosis Phospholipase C Genes and Associations with Extrathoracic Tuberculosis: a Population-Based Study

Y. Kong,1 M. D. Cave,2,3 D. Yang,1 L. Zhang,1 C. F. Marrs,1 B. Foxman,1 J. H. Bates,4,5 F. Wilson,4,5 L. N. Mukasa,4,5 and Z. H. Yang1*

Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan,1 Central Arkansas Veterans Healthcare Center,2 Department of Neurobiology and Developmental Sciences, College of Medicine,3 Department of Epidemiology, College of Public Health, University of Arkansas for Medical Sciences,4 Arkansas Department of Health, Little Rock, Arkansas5

Received 28 June 2005/ Returned for modification 25 July 2005/ Accepted 29 September 2005

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.

* Corresponding author. Mailing address: Epidemiology Department, School of Public Health, University of Michigan, 109 S. Observatory Street, Ann Arbor, MI 48109-2029. Phone: (734) 763-4296. Fax: (734) 764-3192. E-mail: zhenhua{at}umich.edu.

Journal of Clinical Microbiology, December 2005, p. 6048-6053, Vol. 43, No. 12
0095-1137/05/$08.00+0     doi:10.1128/JCM.43.12.6048-6053.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kong, Y., Cave, M. D., Zhang, L., Foxman, B., Marrs, C. F., Bates, J. H., Yang, Z. H. (2007). Association between Mycobacterium tuberculosis Beijing/W Lineage Strain Infection and Extrathoracic Tuberculosis: Insights from Epidemiologic and Clinical Characterization of the Three Principal Genetic Groups of M. tuberculosis Clinical Isolates. J. Clin. Microbiol. 45: 409-414 [Abstract] [Full Text]  
  • Kong, Y., Cave, M. D., Zhang, L., Foxman, B., Marrs, C. F., Bates, J. H., Yang, Z. H. (2006). Population-Based Study of Deletions in Five Different Genomic Regions of Mycobacterium tuberculosis and Possible Clinical Relevance of the Deletions. J. Clin. Microbiol. 44: 3940-3946 [Abstract] [Full Text]  
  • Viana-Niero, C., Rodriguez, C. A. R., Bigi, F., Zanini, M. S., Ferreira-Neto, J. S., Cataldi, A., Leao, S. C. (2006). Identification of an IS6110 insertion site in plcD, the unique phospholipase C gene of Mycobacterium bovis.. J Med Microbiol 55: 451-457 [Abstract] [Full Text]  


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