School of Medicine, Nazarbayev University, Nur-Sultan city, Kazakhstan.
Laboratory of Genomic and Personalized Medicine, National Laboratory Astana, Nazarbayev University, Nur-Sultan city, Kazakhstan.
Mol Biol Rep. 2021 Jan;48(1):691-699. doi: 10.1007/s11033-020-06121-y. Epub 2021 Jan 7.
Lung cavitation is the classic hallmark of TB, which facilitates the disease development and transmission. It involves the degradation of lung parenchyma which is mainly made up of collagen fibers by metalloproteinases (MMPs) produced by activated monocyte-derived cells, neutrophils and stromal cells. The following population-based preliminary case-control study of adults with TB (50) and controls (112) without TB was used to investigate possible association between rs1800012 in COL1A1, rs12722 in COL5A1 genes and pulmonary TB in Kazakhstan. We examined 162 samples (50 cases and 112 controls) to study the associations between TB disease status and demographic variables along with single nucleotide polymorphisms related to COLA1 and COL5A1. The unadjusted χ2 and multivariable logistic regression was performed to find out relationships between SNP and other predictors. Preliminary findings suggest that there is a statistically significant association of age (AOR = 0.97, 95% CI:0.94-0.99, p value = 0.049), social status (AOR = 2.41, 95% CI:1.16-5.02, p value = 0.018), HIV status (AOR = 7.12, 95% CI:1.90-26.7, p value = 0.004) and heterozygous rs12722 SNP (AOR = 2.47, 95% CI:1.17-5.19, p value = 0.018) polymorphism of COL5A1 gene with TB susceptibility. The association of collagen genes with TB pathogenesis indicates that anti TB programs can include development of new drug regimens that include MMP inhibitors which has been found to be helpful in collagen remodeling and repair. Therapeutic targeting of MMPs will prevent extracellular matrix and collagen degradation and granuloma maturation.
肺空洞是结核病的典型特征，有助于疾病的发展和传播。它涉及到由激活的单核细胞衍生细胞、中性粒细胞和基质细胞产生的金属蛋白酶（MMPs）降解肺实质，肺实质主要由胶原蛋白纤维组成。本研究使用基于人群的初步病例对照研究，对哈萨克斯坦的结核病（50 例）和非结核病（112 例）成人进行研究，以探讨 COL1A1 中的 rs1800012、COL5A1 中的 rs12722 与肺结核之间可能存在的关联。我们检查了 162 个样本（50 个病例和 112 个对照），以研究结核病疾病状态与人口统计学变量以及与 COL1A1 和 COL5A1 相关的单核苷酸多态性之间的关系。进行未调整的 χ2 和多变量逻辑回归以确定 SNP 与其他预测因子之间的关系。初步发现表明，年龄（AOR=0.97，95%CI：0.94-0.99，p 值=0.049）、社会地位（AOR=2.41，95%CI：1.16-5.02，p 值=0.018）、HIV 状态（AOR=7.12，95%CI：1.90-26.7，p 值=0.004）和 COL5A1 基因杂合 rs12722 SNP（AOR=2.47，95%CI：1.17-5.19，p 值=0.018）与结核病易感性之间存在统计学显著关联。胶原蛋白基因与结核病发病机制的关联表明，抗结核病计划可以包括开发新的药物方案，包括已发现有助于胶原蛋白重塑和修复的 MMP 抑制剂。MMP 的治疗靶向将阻止细胞外基质和胶原蛋白降解以及肉芽肿成熟。
