Association of Mycobacterium tuberculosis PE_PGRS33 polymorphism with clinical and epidemiological characteristics

• Published in: Tuberculosis (Edinburgh, Scotland) Vol. 87; no. 4; pp. 338 - 346
• Main Authors: Talarico, Sarah, Donald Cave, M, Foxman, Betsy, Marrs, Carl F, Zhang, Lixin, Bates, Joseph H, Yang, Zhenhua
• Format: Journal Article
• Language: English
• Published: Scotland Elsevier Ltd 01.07.2007
• Subjects: Antigens, Bacterial - genetics; Arkansas - epidemiology; Bacterial Proteins - genetics; Cluster Analysis; Clustering; Female; Frameshift Mutation; Genes, Bacterial - genetics; Genetic Variation; Humans; Infectious Disease; Male; Membrane Proteins - genetics; Mycobacterium tuberculosis; Mycobacterium tuberculosis - genetics; Mycobacterium tuberculosis - pathogenicity; PE_PGRS; Peptide Mapping; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Pulmonary/Respiratory; Sequence Analysis, DNA; Seroepidemiologic Studies; Tuberculosis - epidemiology; Tuberculosis - genetics; Arkansas; PE_PGRS; Mycobacterium tuberculosis; Clustering; Genetic variation
• ISSN: 1472-9792; 1873-281X
• DOI: 10.1016/j.tube.2007.03.003

Summary 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.