Polymorphism in Toll-like Receptor 10 and Tuberculosis Susceptibility in Egyptian Population

2021 ◽  
Vol 30 (2) ◽  
pp. 139-144
Author(s):  
AL-Shaimaa M. AL-Tabbakh ◽  
Rehab S. El Sawy ◽  
Marwa S. EL-Melouk

Background: One-third of the world’s population is infected with Mycobacterium tuberculosis. Difference in clinical outcome of infection implies that host genetics may be implicated in such variability. Investigations of Toll-like receptors (TLRs) revealed new information regarding the immunopathogenesis of tuberculosis. Toll-like receptor 2 (TLR2) mediates crucial immune response against Mycobacterium tuberculosis. There is argument that Toll-like receptor (TLR10) participate in tuberculosis susceptibility by acting as a signaling modulator for TLR2. Objectives: The aim of this study was investigating the relationship between TLR 10 SNP 720A/C (rs11096957) and increase susceptibility to tuberculosis. Methodology: Eighty patients with radiological, microbiological and clinical proven active pulmonary tuberculosis (T.B) were included in this study. (TLR10) polymorphisms and allele distributions were compared between these 80 patients and 70 healthy control subjects. Peripheral blood samples were taken from all patients and controls. Genotyping was accomplished by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: When we compare T.B cases with controls, a statistically significant association was observed between T.B susceptibility and SNP 720A/C (rs11096957) in (TLR10). Allele (A) was more frequent in tuberculous cases while allele (C) was more common in controls. It was reported that the AA genotype of (TLR10) SNP rs11096957 was considerably related to the increased risk of developing pulmonary T.B. Homozygosity (AA) has been associated with predisposition to disease by comparing cases to controls (P = 0.045; OR = 2.0; 95% C.I. = 1.0- 4.0). A/C heterozygosity was considerably different in tuberculous cases than in healthy controls with lower risk of developing tuberculosis (P = 0.044; OR = 0.5; 95% C.I. = 0.26 –0.98). Conclusion: TLR10 SNP rs11096957 polymorphism is a risk factor for tuberculosis infection.

2021 ◽  
Vol 11 (5) ◽  
pp. 328
Author(s):  
Michael Leutner ◽  
Nils Haug ◽  
Luise Bellach ◽  
Elma Dervic ◽  
Alexander Kautzky ◽  
...  

Objectives: Diabetic patients are often diagnosed with several comorbidities. The aim of the present study was to investigate the relationship between different combinations of risk factors and complications in diabetic patients. Research design and methods: We used a longitudinal, population-wide dataset of patients with hospital diagnoses and identified all patients (n = 195,575) receiving a diagnosis of diabetes in the observation period from 2003–2014. We defined nine ICD-10-codes as risk factors and 16 ICD-10 codes as complications. Using a computational algorithm, cohort patients were assigned to clusters based on the risk factors they were diagnosed with. The clusters were defined so that the patients assigned to them developed similar complications. Complication risk was quantified in terms of relative risk (RR) compared with healthy control patients. Results: We identified five clusters associated with an increased risk of complications. A combined diagnosis of arterial hypertension (aHTN) and dyslipidemia was shared by all clusters and expressed a baseline of increased risk. Additional diagnosis of (1) smoking, (2) depression, (3) liver disease, or (4) obesity made up the other four clusters and further increased the risk of complications. Cluster 9 (aHTN, dyslipidemia and depression) represented diabetic patients at high risk of angina pectoris “AP” (RR: 7.35, CI: 6.74–8.01), kidney disease (RR: 3.18, CI: 3.04–3.32), polyneuropathy (RR: 4.80, CI: 4.23–5.45), and stroke (RR: 4.32, CI: 3.95–4.71), whereas cluster 10 (aHTN, dyslipidemia and smoking) identified patients with the highest risk of AP (RR: 10.10, CI: 9.28–10.98), atherosclerosis (RR: 4.07, CI: 3.84–4.31), and loss of extremities (RR: 4.21, CI: 1.5–11.84) compared to the controls. Conclusions: A comorbidity of aHTN and dyslipidemia was shown to be associated with diabetic complications across all risk-clusters. This effect was amplified by a combination with either depression, smoking, obesity, or non-specific liver disease.


2014 ◽  
Vol 33 (2) ◽  
pp. 135-141 ◽  
Author(s):  
Hiroya Kanagawa ◽  
Yasuo Niki ◽  
Tami Kobayashi ◽  
Yuiko Sato ◽  
Eri Katsuyama ◽  
...  

2017 ◽  
Vol 102 (5) ◽  
pp. 1249-1259 ◽  
Author(s):  
Upasana Bandyopadhyay ◽  
Attinder Chadha ◽  
Priya Gupta ◽  
Brijendra Tiwari ◽  
Kausik Bhattacharyya ◽  
...  

2018 ◽  
Vol 146 (5) ◽  
pp. 642-647 ◽  
Author(s):  
Xiaochun Jin ◽  
Shuzhou Yin ◽  
Youtao Zhang ◽  
Xu Chen

AbstractToll-like receptor 2 (TLR2) is a key member of TLRs, which is crucial in the initial inflammatory response against bacteria. TLR2, is also the initial barrier against bacterial infection and plays an important role in recognising a variety of bacterial lipoproteins. Several studies have been performed to investigate the TLR2 + 2477G/A polymorphism and bacterial meningitis susceptibility. Unfortunately, the results of previous studies were controversial. Therefore, we performed a meta-analysis to derive a more precise estimation of the association. The association between the TLR2 + 2477G/A polymorphism and bacterial meningitis susceptibility was assessed by odds ratios together with their 95% confidence intervals (CI). Six studies were enrolled in the present meta-analysis. Overall, no significant association between TLR2 + 2477G/A polymorphism and bacterial meningitis risk were found under allele contrast (A vs. G: OR = 1.15, 95% CI = 0.93–1.43, P = 0.202), recessive genetic model (AA vs. AG/GG: OR = 1.12, 95% CI = 0.90–1.41, P = 0.313). The significant association was found between TLR2 + 2477G/A polymorphism and pneumococcal meningitis risk under allele contrast (A vs. G: OR = 1.54, 95% CI = 1.01–2.36, P = 0.046), recessive genetic model (AA vs. AG/GG: OR = 1.63, 95% CI = 1.03–2.57, P = 0.035). We conclude that TLR2 + 2477G/A polymorphism is not associated with meningococcal meningitis risk but contributes an increased risk of pneumococcal meningitis.


2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Xiao-li Liu ◽  
Jian-zong Du ◽  
Yu-miao Zhou ◽  
Qin-fen Shu ◽  
Ya-guo Li

Clinical and experimental data have demonstrated that inflammation plays fundamental roles in the pathogenesis of ischemic stroke. Interleukin-16 (IL-16) is identified as a proinflammatory cytokine that is a key element in the ischemic cascade after cerebral ischemia. We aimed to examine the relationship between theIL-16polymorphisms and the risk of ischemic stroke in a Chinese population. A total of 198 patients with ischemic stroke and 236 controls were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing method. We found that the rs11556218TG genotype and G allele ofIL-16were associated with significantly increased risks of ischemic stroke (TG versus TT, adjusted OR = 1.88; 95% CI, 1.15–3.07; G versus T, adjusted OR = 1.54; 95% CI, 1.05–2.27, resp.). However, there were no significant differences in the genotype and allele frequencies ofIL-16rs4778889 T/C and rs4072111 C/T polymorphisms between the two groups, even after stratification analyses by age, gender, and the presence or absence of hypertension, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia. These findings indicate that theIL-16polymorphism may be related to the etiology of ischemic stroke in the Chinese population.


2015 ◽  
Vol 83 (6) ◽  
pp. 2242-2254 ◽  
Author(s):  
Edward T. Richardson ◽  
Supriya Shukla ◽  
David R. Sweet ◽  
Pamela A. Wearsch ◽  
Philip N. Tsichlis ◽  
...  

Mycobacterium tuberculosissurvives within macrophages and employs immune evasion mechanisms to persist in the host. Protective T helper type 1 (Th1) responses are induced, and the immune response in most individuals is sufficient to restrictM. tuberculosisto latent infection, but most infections are not completely resolved. As T cells and macrophages respond, a balance is established between protective Th1-associated and other proinflammatory cytokines, such as interleukin-12 (IL-12), interferon gamma (IFN-γ), and tumor necrosis factor alpha, and anti-inflammatory cytokines, such as IL-10. The mechanisms by whichM. tuberculosismodulates host responses to promote its survival remain unclear. In these studies, we demonstrate thatM. tuberculosisinduction of IL-10, suppression of IL-12, and inhibition of class II major histocompatibility complex (MHC-II) molecules in infected macrophages are all driven by Toll-like receptor 2 (TLR2)-dependent activation of the extracellular signal-regulated kinases (ERK). Elimination of ERK signaling downstream of TLR2 by pharmacologic inhibition with U0126 or genetic deletion ofTpl2blocks IL-10 secretion and enhances IL-12 p70 secretion. We demonstrate thatM. tuberculosisregulation of these pathways in macrophages affects T cell responses to infected macrophages. Thus, genetic blockade of the ERK pathway inTpl2−/−macrophages enhances Th1 polarization and IFN-γ production by antigen-specific CD4+T cells responding toM. tuberculosisinfection. These data indicate thatM. tuberculosisand its potent TLR2 ligands activate ERK signaling in macrophages to promote anti-inflammatory macrophage responses and blunt Th1 responses against the pathogen.


2020 ◽  
Author(s):  
hosnie hoseini ◽  
Parichehreh Yaghmaei ◽  
Gholamreza Bahari ◽  
saeed aminzadeh

Abstract Background, Programed cell death 1 (PD-1) and its ligand (PD-L1) activity have already detected in various cancers. In non-Hodgkin lymphoma (NHL), however, the prognostic value of PD-1/PD-L1 genes polymorphisms and expression levels remains unclear. In the present study we aimed to investigate the relationship between genetic polymorphisms of PD-1/PD-L1 genes and non-Hodgkin lymphoma in Iranian papulation. Methods , four single nucleotide polymorphisms of the PD-1/PD-L1 genes, including 134 NHL patients and 125 healthy controls were examined using PCR-RFLP method. The expression level of PD-1/PD-L1 genes were analyzed using real time PCR method. Results , our data demonstrated that the PD-L1 rs2890685 (A>C) SNP (p<0.0001) significantly was associated with increased risk of NHL. The AA genotype of PD-L1 rs2890685 polymorphism was found to be more prevalent in NHL patents compared to healthy controls. No significant association were found between PD-L1 rs4143815, PD-1 rs11568821, PD-1rs2227981 SNPs and the risk of NHL incidence. Furthermore, our data showed that the mRNA transcription levels of both PD-1 and PD-L1 were significantly higher than normal healthy controls (p<0.001). Conclusion , Collectively, our finding demonstrated that the functional PD-L1 rs2890685 polymorphism was associated with NHL risk, suggesting that genetic variant of PD-L1 might be a possible prognosis marker for prediction of NHL risk and its development.


MicroRNA ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 216-223
Author(s):  
Mahsa Azizi ◽  
Nahid Rahimi ◽  
Gholamreza Bahari ◽  
Seyed Mehdi Hashemi ◽  
Mohammad Hashemi

Aims: This study aimed at examining the effect of 3-bp pre-miR-3131 insertion/deletion (ins/del) polymorphism on Breast Cancer (BC) risk. Objectives: Totally 403 women including 199 BC patients and 204 women who have no cancer were included in this case-control study. Genotyping of miR-3131 3-bp ins/del polymorphism was performed by mismatch PCR-RFLP method. Methods: The findings expressed that the pre-miR-3131 3-bp ins/del variant was not related to the risk of BC in all genetic tested models. While, the ins/del genotype was related to late onset BC (OR=2.53, 95%CI=1.27-4.84, p=0.008). Results: Pooled results from the meta-analysis indicated to that the pre-miR-3131 ins/del is related to with an increased risk of cancer in heterozygous (OR=1.26, 95%CI=1.06-1.51, p=0.01), dominant (OR=1.33, 95%CI=1.14-1.54, p=0.0002), and allele (OR=1.24, 95%CI=1.06-1.45, p=0.006) genetics models. Conclusion: It is concluded that, our findings did not support a relationship between pre-miR-3131 ins/del polymorphism and the risk of BC. While, this variant was significantly related to late onset BC. Combined results of this study with previous studies indicated that this polymorphism increased the risk of cancer. More studies in a study with larger population with variety of ethnicities are required to verify our findings.


2019 ◽  
Vol 2019 ◽  
pp. 1-6 ◽  
Author(s):  
Zhenzhen Fang ◽  
Di Che ◽  
Shuang Qing ◽  
Qingfeng Li ◽  
Hui Men ◽  
...  

Genetic susceptibility may be involved in the onset of recurrent miscarriage. Previous studies have shown that some genetic polymorphisms that regulate cell migration are associated with susceptibility to recurrent miscarriage. The SOX2 overlapping transcript (SOX2OT) may regulate the migration and invasion of multiple tumor cells and is related to susceptibility to various diseases. However, whether lncRNA SOX2OT polymorphisms are related to recurrent miscarriage susceptibility is unclear. Therefore, we investigated the relationship between the lncRNA SOX2OT rs9839776 C>T polymorphism and recurrent miscarriage susceptibility. We recruited 570 subjects with recurrent miscarriage and 578 healthy control subjects from a population in southern China and used the TaqMan method for genotyping. We found a significant association between the rs9839776 CT genotype in the SOX2OT gene and an increased risk for recurrent miscarriage (CT vs CC: adjusted OR=1.357, 95%CI=1.065−1.728, P=0.0134). However, we did not observe any significant associations between the recurrent miscarriage risk and the number of miscarriages in different age groups. In conclusion, our study indicated that the rs9839776 CT genotype may contribute to an increased risk of recurrent miscarriage in the southern Chinese population and that rs9839776 may act as a prognostic biomarker in recurrent miscarriage patients. However, an experiment-based study with a larger sample size should be performed to confirm these results.


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