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.
Introduction. Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology that leads to disability due to articular and extra-articular damage. RA prevalence is variable. The disease is most common among females with a 3 : 1 ratio. The interaction of environmental and host factors contributes to RA development. Currently, the genome-wide association studies (GWAS) give the opportunity to uncover the RA genetic background. Anticitrullinated peptide antibody (ACPA) is a highly specific RA antibody, associated with poor prognosis and severe course of RA, and regulated by numerous genes. Our study is aimed at investigating whether there are any clinical and genetic aspects correlate with ACPA presence in Kazakhstani patients with RA. Indeed, the available studies on this subject are focused on Caucasian and East Asian populations (mainly Japanese and Chinese), and there are scarce data from Central Asia. Methods. Our study included 70 RA patients. Patients’ blood samples were collected and genotyped for 14 SNPs by real-time polymerase chain reaction (RT-PCR). General examination, anamnestic, and clinical and laboratory data collection were carried out. Statistical analysis was performed using R statistics. Results and Conclusion. Our study revealed a significant association of ACPA positivity with Fc receptor-like 3 (FCRL3) and ACPA negativity with signal transducer and activator of transcription 4 (STAT4) genes, but not with T cell activation Rho GTPase activating protein (TAGAP). In addition, ACPA positivity was associated with radiographic progression, rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), age of RA onset, the patient global assessment, body mass index (BMI), and Gamma globulin. Conclusion. Remained 11 earlier identified significantly associated in Caucasian and Asian population SNPs were not replicated in our cohort. Further studies on larger cohorts are needed to confirm our findings with higher confidence levels and stronger statistical power.
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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