Article

Association of Mycobacterium tuberculosis PE PGRS33 polymorphism with clinical and epidemiological characteristics.

Department of Epidemiology, School of Public Health, University of Michigan, 109 Observatory Street, 4648 SPH I, Ann Arbor, MI 48109, USA.
Tuberculosis (impact factor: 3.47). 08/2007; 87(4):338-46. DOI:10.1016/j.tube.2007.03.003 pp.338-46
Source: PubMed

ABSTRACT There is evidence that some members of the Mycobacterium tuberculosis PE PGRS gene subfamily, including PE PGRS33, may have a specific function in M. tuberculosis persistence. The impact of naturally-occurring PE PGRS33 genetic variations on the virulence and transmissibility of clinical M. tuberculosis isolates is not known. We used PCR and DNA sequencing to identify genetic variations in the PE PGRS33 gene in comparison with the sequenced laboratory strain, H37Rv, among 649 isolates from a population-based sample. The PE PGRS33 alleles were placed into two groups, based on the effect of the sequence variations on the PE PGRS33 protein, and their associations with clinical and epidemiological characteristics were assessed using multivariate logistic regression to control for potential confounding of host-related factors. Of the 639 isolates for which sequence data were obtained, 139 (21.8%) had PE PGRS33 alleles that would result in a significant change to the PE PGRS33 protein due to large insertions/deletions or frameshift mutations. These isolates were significantly associated with clustering based on genotype and absence of cavitations in the lungs, compared to isolates having PE PGRS33 alleles that would result in no or minimal change to the PE PGRS33 protein. The association of significant changes to PE PGRS33 with clinical and epidemiological characteristics suggests that PE PGRS33 may have an important role in M. tuberculosis persistence.

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Keywords

clinical M. tuberculosis
 
genetic variations
 
genotype
 
host-related factors
 
large insertions/deletions
 
M. tuberculosis persistence
 
minimal change
 
multivariate logistic regression
 
Mycobacterium tuberculosis PE PGRS gene subfamily
 
naturally-occurring PE PGRS33 genetic variations
 
PE PGRS33
 
PE PGRS33 alleles
 
PE PGRS33 gene
 
PE PGRS33 protein
 
population-based sample
 
sequence data
 
sequence variations
 
sequenced laboratory strain
 
significant change
 
specific function