Elsevier

Tuberculosis

Volume 89, Issue 1, January 2009, Pages 68-70
Tuberculosis

Effect of matrix metalloproteinase-9 −1562C/T gene polymorphism on manifestations of pulmonary tuberculosis

https://doi.org/10.1016/j.tube.2008.08.001Get rights and content

Summary

Increased levels of matrix metalloproteinase-9 (MMP-9) in patients with tuberculous meningitis, tuberculous pleuritis, and advanced pulmonary tuberculosis (TB) suggest a pivotal role for MMP-9 in the development of pulmonary TB and its clinical manifestations. The present study was performed to evaluate the role of the −1562C/T single nucleotide polymorphism (SNP) in the promoter region of the human MMP-9 gene in development of pulmonary TB and its radiographic characteristics. A case–control study was performed with a study population of 205 patients with pulmonary TB and 223 healthy controls. Differences were explored in the allele and genotype distributions of the −1562C/T polymorphism between patients with pulmonary TB and healthy controls, between patients with single- and multi-lobe involvement, and between patients with and without cavities. The −1562C/C genotype was more common in patients with multi-lobe involvement than in those with single-lobe involvement (81.8 vs. 67.6%, P = 0.03). However, there were no significant differences in the distribution between patients with pulmonary TB and healthy controls (P = 0.40) or between patients with and without cavities (P = 0.18). These results suggest that the −1562C/C genotype is associated with the intrapulmonary spread of TB rather than its development.

Introduction

Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that have important physiological roles, including remodeling of the extracellular matrix, facilitating cell migration, cleaving cytokines, and activating defensins.1 Dysregulated MMP activity is implicated in the pathology of pulmonary diseases, including lung cancer, asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, sarcoidosis, and tuberculosis (TB).1

Of the 23 known MMPs,2 MMP-9 (also known as 92-kDa type IV collagenase or gelatinase) is active against gelatins and type IV collagen.3 As MMP-9 knock-out mice showed increased susceptibility to Staphylococcus aureus-triggered septic arthritis4 and Escherichia coli peritonitis,5 MMP-9 appears to play a pivotal role in human defense against microorganisms. In addition, increased levels of MMP-9 have been reported in patients with tuberculous meningitis,6, 7, 8 tuberculous pleuritis,9, 10 and advanced pulmonary TB.11

In this context, we examined the role of the −1562C/T single nucleotide polymorphism (SNP) in the promoter region of the human MMP-9 gene, which was shown to be associated with upper lung-dominant emphysema12 and the severity of coronary atherosclerosis,13 in the development of pulmonary TB and its radiographic characteristics and extent.

Section snippets

Determination of the sample size

To calculate the minimum sample size, we used the following values: prevalence of −1562T in healthy controls, 15% based on a pilot study; alpha error, 0.05; power, 0.80; and expected difference, 15%. Using these parameters and assumptions, the minimum sample size for each group was estimated to be 134.

Participants

DNA samples from 205 patients with bacteriologically or pathologically confirmed pulmonary TB were used. Patients with a positive human immunodeficiency virus test and those receiving

Baseline clinical characteristics of the participants

Table 1 presents the baseline characteristics of the participants. The median age of the 205 patients with pulmonary TB was 42 years, and 118 patients (57.6%) were male. Of the patients with TB, 137 (66.8%) had multi-lobe involvement and 83 (40.5%) had cavities. The median age of the 223 healthy controls was 26 years, and 143 (64.1%) were male (Table 1).

Distribution of the −1562C/T alleles and genotypes in TB patients and controls

The MMP-9 genotypes in both groups showed Hardy–Weinberg equilibrium. Neither the alleles nor genotypes were distributed differently between

Discussion

Only 10% of those infected with Mycobacterium tuberculosis develop clinical TB, and only a few cases have obvious risk factors, suggesting that genetic traits play a role in the pathogenesis of this disease.17 This assumption is also supported by a higher concordance rate of TB in monozygotic twins than in dizygotic twins.18 In fact, a large number of SNPs on various genes have been reported to be associated with the development of TB.19

SNPs of the MMP-9 gene could be candidates for genetic

References (23)

  • D. Iglesias et al.

    Metalloproteinases and tissue inhibitors of metalloproteinases in exudative pleural effusions

    Eur Respir J

    (2005)
  • Cited by (15)

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