Background: 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. Objective: The following population-based preliminary case-control study of adults with TB and controls without TB will check the possible association between rs1800012 in COL1A1, rs1272222 in COL5A1 genes to human TB susceptibility in Kazakhstan. Methods: In this case-control study including 165 samples we examined the associations between TB disease status and demographic variables along with single nucleotide polymorphisms related to COLA1 and COL5A1. The unadjusted χ2 and adjusted logistic regression was performed to find out relationships between SNPS and other predictors. Results: Preliminary findings suggest that there is a statistically significant association of age (OR=0.44, 95% CI:0.21-0.92, p-value=0.03) , social status (OR=0.42, 95% CI:0.201 -0.87, p-value=0.020), HIV status(OR=6.9, 95% CI:1.86 - 25.6, p-value=0.004) and heterozygous rs12722 SNP (OR=2.45, 95% CI:1.16 -5.16 p-value=0.019) polymorphism of COL5A1 gene with TB susceptibility. Conclusion: The association of collagen genes with TB pathogenesis indicates that anti TB programs should develop new drug regimens that include MMP inhibitors. Therapeutic targeting of MMPs will prevent extracellular matrix degradation and granuloma maturation.
Background: 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 monocytederived cells, neutrophils and stromal cells. Objective: The following population-based preliminary case-control study of adults with TB and controls without TB will check the possible association between rs1800012 in COL1A1, rs1272222 in COL5A1 genes to human TB susceptibility in Kazakhstan. Methods: In this case-control study including 165 samples we examined the associations between TB disease status and demographic variables along with single nucleotide polymorphisms related to COLA1 and COL5A1. The unadjusted χ2 and adjusted logistic regression was performed to find out relationships between SNPS and other predictors. Results: Preliminary findings suggest that there is a statistically significant association of age (OR=0.44, 95% CI:0.21-0.92, p-value=0.03) , social status (OR=0.42, 95% CI:0.201 -0.87, p-value=0.020), HIV status(OR=6.9, 95% CI:1.86 -25.6, p-value=0.004) and heterozygous rs12722 SNP (OR=2.45, 95% CI:1.16 -5.16 p-value=0.019) polymorphism of COL5A1 gene with TB susceptibility. Conclusion:The association of collagen genes with TB pathogenesis indicates that anti TB programs should develop new drug regimens that include MMP inhibitors. Therapeutic targeting of MMPs will prevent extracellular matrix degradation and granuloma maturation.
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