Lysosomal acid lipase gene single nucleotide polymorphism and pulmonary tuberculosis susceptibility.

BACKGROUND: The factors that predispose to pulmonary tuberculosis (PTB) are not fully understood, However. Gene polymorphisms have been associated with PTB development. OBJECTIVES: In this study, we investigated the relationship between LIPA gene polymorphisms and a predisposition to pulmonary tuberculosis caused by Mycobacterium tuberculosis. METHODS: A total of 202 cases of PTB and 218 healthy controls (HCS) were included in this study. Analyses were done under allelic, homozygous, and heterozygous, dominant, recessive models, and were used to calculate values, odds ratios (ORs), and 95% confidence intervals (CIs) for assessing the association between single nucleotide polymorphisms (SNPs) and disease risk. Genotyping was conducted using the real time polymerase chain reaction with high resolution melting curve analysis. RESULTS: When comparing PTB patients with healthy controls (HCS), significant associations with disease development were observed for both SNPs rs1051338 and rs7922269. Analysis was done based on models of genetic inheritance in man that is co-dominant, recessive and dominant models. Rs1051338, the heterozygous (AC vs. AA) P: 0.001, OR: 1.998, 95% CI: 1.312-3.042 and homozygous (CC vs. AA) P: < 0.001, OR: 4.078, 95% CI: 2.134-7.796 Co-dominant associated with increased risk for the disease. Under recessive (CC vs. AA + AC), P: 0.001, OR: 2.829: 95% CI: 1.543-5.185 and dominant model (AC + CC vs. AA) P: < 001, OR: 2.331, 95% CI: 1.564-3.474 the genotypes distribution increased the individual risk, plus its alleles distribution (P: < 0.001, OR: 2.004, 95% CI: 1.505-2.669). Considering SNP rs7922269 mutation significantly increased pulmonary tuberculosis risk as was observed in the homozygous GG vs. TT (P: 0.003, OR: 3.162, 95% CI: 1.431-6.989); heterozygous GT vs. TT (P: < 0.001, OR: 1.2.259, 95% CI: 1.503-3.394); dominant model (GT + GG vs. TT; P: < 0.001, OR: 2.061, 95% CI: 1.402-3.032) and the allele G (P: < 0.001, OR: 1.829, 95% CI:1.361-2.458), however no significant association was observed in the Recessive model (GG vs. TT + GT; P: 0.057, OR: 2.568, 95% CI: 0.965-4.432). CONCLUSION: The findings of our study strengthen the hypothesis that LIPA rs1051338 and rs7922269 polymorphism associated with increased risk for pulmonary Tb in a sample of northern Chinese population.

Empagliflozin Protects Against Proximal Renal Tubular Cell Injury Induced by High Glucose via Regulation of Hypoxia-Inducible Factor 1-Alpha.

BACKGROUND: Evidence from both animal and human studies clearly supports the renal beneficial effects of empagliflozin (emp), a sodium glucose co-transporter 2 (SGLT2) inhibitor, but the mechanism in which it exerts its effect is not well understood. In this study, we investigated the capability of emp on reducing hyperglycemia-induced renal proximal tubular epithelial cells injury and we evaluated if the renoprotective effect of emp associates with hypoxia-inducible factor-1α (HIF-1α). MATERIALS AND METHODS: Human kidney cell lines (HK-2 cells) were incubated in normoxia, high glucose with or without emp treatment for 72 hours to evaluate the induction of HIF-1α, glucose transporter-1, SGLT2, the fibrosis signal pathway and epithelial-mesenchymal transition (EMT) markers. RESULTS: High glucose (HG) increased expression of Collagen IV, Fibronectin, transforming growth factor-beta1 (TGF-ß1). However, emp treatment remarkably decreased expression of TGF-ß1, accumulation of extracellular matrix proteins (Fibronectin, Collagen IV), as well as (phosphorylated-smad3) P-smad3. HG increased SGLT2 protein expression compared to normal glucose (NG) while emp significantly decreased SGLT2 expression. Furthermore, emp decreased high glucose-induced alpha-smooth muscle actin (α-SMA) expression and reversed epithelial marker (E-catherin) suppression induced by high glucose. In addition, emp treatment for 72 h increased expression of HIF-1α protein (95% CI: -0.5918 to -0.002338, at 100nM, P < 0.05, 95% CI -0.6631 to -0.07367 at 500nM, P < 0.05) in hyperglycemic normoxic HK-2 cells. Furthermore, we observed increased expression of GLUT-1 protein after emp treatment and remarkably decreased cell proliferation. CONCLUSION: Emp treatment protected proximal renal tubular cells injury induced by high glucose. Induction of HIF-1α expression by emp may play an essential role in the protection of high glucose-induced proximal renal tubular epithelial cells injury.

Association between CLEC4E gene polymorphism of mincle and pulmonary tuberculosis infection in a northern Chinese population.

BACKGROUND: Pulmonary tuberculosis caused by an intracellular pathogen, Mycobacterium tuberculosis continues to exist as a hazardous disease to human life globally. Genetic polymorphisms regulate resistance and susceptibility to tuberculosis. The C-type lectin receptor of family 4 member E (CLEC4E) confers protection against tuberculosis in laboratory animals but its function in influencing exposure or resistance to pulmonary tuberculosis (PTB) in humans remains obscure. AIM: We conducted this research to analyze the effects or concomitance of CLEC4E gene variations with susceptibility to pulmonary tuberculosis in a northern Chinese population. METHOD: In this study, 202 participants with pulmonary tuberculosis and 214 controls without PTB were enrolled. Two single nucleotide polymorphisms (SNPs) for CLEC4E on chromosome 12 were selected with a minor allele frequency of >0.05. All the SNPs were genotyped using high resolution melting analysis-PCR. RESULTS: We estimated and compared two SNPs, rs10841845 and rs10841847. From our study findings, CLEC4E rs10841845 conferred protection against the development of pulmonary TB with a P value of <0.05 and odds ratio of <1 for all models of genetic inheritance. CLEC4E rs10841847 genotypes in co-dominant, Recessive, Dominant models and alleles had a significant statistical difference between patients and controls associated with resistance against the development of PTB (P<0.05 and OR<1). CONCLUSION: Our findings suggest that variations at rs10841845 and rs10841847 of CLEC4E genes are associated with increased individual protection against PTB.