This Article Full Text Full Text (PDF) All Versions of this Article: 200408-1147OCv1 171/12/1436    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yang, Z. Articles by Cave, M. D. Search for Related Content PubMed PubMed Citation Articles by Yang, Z. Articles by Cave, M. D.

Clinical Relevance of Mycobacterium tuberculosis plcD Gene Mutations

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

Correspondence and requests for reprints should be addressed to Zhenhua Yang, M.D., Ph.D., Epidemiology Department, School of Public Health, University of Michigan, 109 S. Observatory Street, Ann Arbor, MI 48109-2029. E-mail: zhenhua{at}umich.edu

To identify Mycobacterium tuberculosis virulence factors, we integrated comparative genomics and epidemiologic data analysis to investigate the relationship between certain genomic insertions and deletions in the phospholipase-C gene D (plcD) with the clinical presentation of tuberculosis (TB). Four hundred ninety-six well-characterized M. tuberculosis clinical isolates were studied. Approximately 30% (147) of the isolates had an interruption of the plcD gene. Patients infected with the plcD mutant were twice as likely to have extrathoracic disease as those infected by a strain without an interruption (adjusted odds ratio, 2.19; 95% confidence interval, 1.27, 3.76). When we limited the analysis to the 275 isolates with distinct DNA fingerprint patterns, we observed the same association (adjusted odds ratio, 2.74; 95% confidence interval, 1.35, 5.56). Furthermore, the magnitude of the association appeared to differ with the type of extrathoracic TB. Our findings suggest that the plcD gene of M. tuberculosis is potentially involved in the pathogenesis of TB, and the clinical presentation of the disease may be influenced by the genetic variability of the plcD region.

Key Words: extrathoracic tuberculosis • pathogenesis • virulence factors

This article has been cited by other articles:

				G. Thwaites, M. Caws, T. T. H. Chau, A. D'Sa, N. T. N. Lan, M. N. T. Huyen, S. Gagneux, P. T. H. Anh, D. Q. Tho, E. Torok, et al. Relationship between Mycobacterium tuberculosis Genotype and the Clinical Phenotype of Pulmonary and Meningeal Tuberculosis J. Clin. Microbiol., April 1, 2008; 46(4): 1363 - 1368. [Abstract] [Full Text] [PDF]

				A. M. Hebert, S. Talarico, D. Yang, R. Durmaz, C. F. Marrs, L. Zhang, B. Foxman, and Z. Yang DNA Polymorphisms in the pepA and PPE18 Genes among Clinical Strains of Mycobacterium tuberculosis: Implications for Vaccine Efficacy Infect. Immun., December 1, 2007; 75(12): 5798 - 5805. [Abstract] [Full Text] [PDF]

				Y. Kong, M. D. Cave, L. Zhang, B. Foxman, C. F. Marrs, J. H. Bates, and Z. H. Yang 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., February 1, 2007; 45(2): 409 - 414. [Abstract] [Full Text] [PDF]

				D. Alland, D. W. Lacher, M. H. Hazbon, A. S. Motiwala, W. Qi, R. D. Fleischmann, and T. S. Whittam Role of Large Sequence Polymorphisms (LSPs) in Generating Genomic Diversity among Clinical Isolates of Mycobacterium tuberculosis and the Utility of LSPs in Phylogenetic Analysis J. Clin. Microbiol., January 1, 2007; 45(1): 39 - 46. [Abstract] [Full Text] [PDF]

				Y. Kong, M. D. Cave, L. Zhang, B. Foxman, C. F. Marrs, J. H. Bates, and Z. H. Yang Population-Based Study of Deletions in Five Different Genomic Regions of Mycobacterium tuberculosis and Possible Clinical Relevance of the Deletions J. Clin. Microbiol., November 1, 2006; 44(11): 3940 - 3946. [Abstract] [Full Text] [PDF]

				C. Viana-Niero, C. A. R. Rodriguez, F. Bigi, M. S. Zanini, J. S. Ferreira-Neto, A. Cataldi, and S. C. Leao Identification of an IS6110 insertion site in plcD, the unique phospholipase C gene of Mycobacterium bovis. J. Med. Microbiol., April 1, 2006; 55(Pt 4): 451 - 457. [Abstract] [Full Text] [PDF]

				W. W. Yew and C. C. Leung Update in tuberculosis 2005. Am. J. Respir. Crit. Care Med., March 1, 2006; 173(5): 491 - 498. [Full Text] [PDF]

				Y. Kong, M. D. Cave, D. Yang, L. Zhang, C. F. Marrs, B. Foxman, J. H. Bates, F. Wilson, L. N. Mukasa, and Z. H. Yang Distribution of Insertion- and Deletion-Associated Genetic Polymorphisms among Four Mycobacterium tuberculosis Phospholipase C Genes and Associations with Extrathoracic Tuberculosis: a Population-Based Study J. Clin. Microbiol., December 1, 2005; 43(12): 6048 - 6053. [Abstract] [Full Text] [PDF]