Correlation Between Gene Polymorphisms and Levels of Serum Matrix Metalloproteinases with Cavitary Features and Pulmonary Fibrosis of the Patient Tuberculosis Multi-Drug Resistance Using High-Resolution Computerized Tomography of the Thorax

Abstract

Matrix metalloproteinases (MMPs) are proteins that play a role in the inflammatory and remodeling processes caused by infections, including pulmonary tuberculosis (TB), especially multidrug resistance. This study aims to correlate the relationship between serum levels and polymorphism of MMP-1 and MMP-9 with cavity characteristics, such as number, diameter, wall thickness as well as distribution of fibrosis in Multidrug-Resistant (MDR)- and Drug-Sensitive (DS)-TB patients. This study used a comparative cross-sectional study design. The subjects came from outpatients at Abdoel Moelok Hospital, Lampung Indonesia had passed the ethical test. Subjects were divided into two groups, 34 subjects in the MDR-TB group and 36 subjects in the DS-TB group. The levels of MMP-1 and MMP-9 were carried out by ELISA test, genotype of MMP-1 and MMP-9 were determined using PCR-Sequencing method. In addition, cavities and fibrosis were measured using thoracic High-Resolution Computerized Tomography (HRCT) imaging. There was significant difference in the number of cavities more than 6, 6 mm in diameter, as well as cavity thickness in MDR-TB compared to DS-TB patients. Fibrosis distribution in lung segments was also different significantly in MDR-TB compared to DS-TB. Although MMP-9 levels in the MDR-TB group were highest than in the DS-TB group, there was no statistically significant. This study showed that there was a correlation between MDR-TB and DS-TB regarding the number of cavities, cavity diameter, cavity wall thickness, and distribution of fibrosis in the affected lung segments as measured by HRCT. There was no correlation between MMP-1 (-1607G) and MMP-9 (C1562T) genotypes and MMP-1 and MMP-9 serum levels, the MMP‑1 genotype in the two study groups differed significantly and was a risk factor for five times the incidence of MDR-TB. In addition, there was a substantial difference in cavity wall thickness between the G/G MMP-1 1607 genotype and the T/T MMP-9 genotype in the two study groups.