Clinical relevance of Mycobacterium tuberculosis plcD gene mutations.
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.
Yang
Zhenhua
Z
Epidemiology Department, School of Public Health, University of Michigan, 109 S. Observatory Street, Ann Arbor, MI 48109-2029, USA. zhenhua@umich.edu
Yang
Dong
D
Kong
Ying
Y
Zhang
Lixin
L
Marrs
Carl F
CF
Foxman
Betsy
B
Bates
Joseph H
JH
Wilson
Frank
F
Cave
M Donald
MD
D000328:Adult; D000368:Aged; D015139:Blotting, Southern; D016172:DNA Fingerprinting; D018450:Disease Progression; D005260:Female; D005798:Genes, Bacterial / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009169:Mycobacterium tuberculosis / Q000235:genetics* / Q000472:pathogenicity*; D016133:Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D012720:Severity of Illness Index; D014376:Tuberculosis / Q000382:microbiology* / Q000503:physiopathology; D010738:Type C Phospholipases / Q000235:genetics* / Q000378:metabolism
D005819:Genetic Markers; D010738:Type C Phospholipases