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Published ahead of print on April 1, 2005, doi:10.1164/rccm.200408-1147OC

Am. J. Respir. Crit. Care Med., Volume 171, Number 12, June 2005, 1436-1442

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Submitted on August 31, 2004
Accepted on March 23, 2005

Clinical Relevance of Mycobacterium tuberculosis plcD Gene Mutations

Zhenhua Yang1*, Dong Yang1, Ying Kong1, Lixin Zhang1, Carl F Marrs1, Betsy Foxman1, Joseph H Bates2, Frank Wilson2, and M. Donald Cave3

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

* To whom correspondence should be addressed. E-mail: zhenhua{at}umich.edu.

In order to identify Mycobacterium tuberculosis virulence actors, we integrated comparative genomics and epidemiological data analysis to investigate the relationship between certain genomic insertions and deletions in the phopholipase 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: Virulence factors, Pathogenesis, Extrathoracic tuberculosis




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