Effect of matrix metalloproteinase-9 −1562C/T gene polymorphism on manifestations of pulmonary tuberculosis
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.
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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
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Toll-like receptor and matrix metalloproteinase single-nucleotide polymorphisms, haplotypes, and polygenic risk score differentiated between tuberculosis disease and infection
2022, International Journal of Infectious DiseasesCitation Excerpt :For the MMP SNPs, the -1607 MMP1 functional polymorphism genotype 2G/2G increased the risk of active TB, with the joint effect of monocyte chemoattractant protein-1 genotype GG in Mexicans and Peruvians in one previous study (Ganachari et al., 2010). Also, another study revealed that the -1562C/T SNP in the promoter region of the MMP9 gene was associated with multilobar lesions of TB, indicating its role in intrapulmonary spread (Lee et al., 2009). The association between MMP8 SNPs and TB disease status warrants further investigation.
Gene polymorphism of matrix metalloproteinases 3 and 9 in breast cancer
2016, Gene ReportsCitation Excerpt :The second SNP is insertion/deletion of adenosine (6A/5A) at position − 1171 in the promoter sequence of MMP3 located on 11q21–23 (Okamoto et al., 2010). The distribution of genetic variants of MMP3 and MMP9 differs between various populations as Indian, Japanese, Korean, Chinese, Italy, Sweden, Caucasian and African-American populations (Hirakawa et al., 2003; Kubben et al., 2006; Woo et al., 2007; Xing et al., 2007; Ghilardi et al., 2002, Lei et al., 2002, Lee et al., 2009). Several studies have demonstrated that 1562 C/T and 1171 6A/5A polymorphisms in the promoter regions of MMP9 and MMP3 respectively result in modulation of binding affinity of transcription factors with subsequent on gene expression (Ye, 2000, Jormsjo et al., 2001, Rahimi et al., 2015).
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