Genetic diversity of TLR2, TLR4, and VDR loci and pulmonary tuberculosis in Moroccan patients

Arji, Naima; Busson, Marc; Iraqi, G.; Bourkadi, Jamal Eddine; Benjouad, Abdelaziz; Bouayad, Abdellatif; Mariaselvam, Christina Mary; Salah, Samir; Fortier, Catherine; Amokrane, Kahina; Marzais, François; Boukouaci, Wahid; Krishnamoorthy, Rajagopal; Charron, Dominique; Aouad, Rajae El; Tamouza, Ryad

doi:10.3855/jidc.3820

Cited by 37 publications

(22 citation statements)

References 63 publications

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“…We found rs3804099 was not associated with both PTB and LTBI after Bonferroni correction. Our finding was partly similar to the data from a previous study on Mexican patients (24). Indeed, their study suggested that this genotype did not influence the susceptibility to PTB, while the CT genotype was related to TB.…”

Section: Discussionsupporting

confidence: 92%

Evaluation of TLR2,TLR4, and TOLLIP polymorphisms for their role in tuberculosis susceptibility

Huang

Wang

et al. 2018

APMIS

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Previous studies indicated that single-nucleotide polymorphisms (SNPs) of genes coding for toll-like receptors (TLRs) and toll-interacting protein (TOLLIP) may be involved in the pathogenesis of pulmonary tuberculosis (PTB). This study was designed to investigate potential associations between the polymorphisms in TLR2, TLR4, and TOLLIP and susceptibility to latent tuberculosis infection (LTBI) or subsequent PTB in a Chinese Han population. A total of 209 PTB and 201 LTBI patients and 204 healthy control subjects (HCS) were enrolled in our study. We performed a logistic regression including sex and age as covariates to test the effect of genotype. Genotyping was conducted using the improved multiplex ligase detection reaction (iMLDR). Eleven markers in TLR2, TLR4, and TOLLIP were assessed. No significant association between polymorphisms of TLR2 and TLR4 with PTB or LTBI was detected. For TOLLIP, rs5743899 (p = 0.005, OR = 1.83, 95% CI: 1.20-2.80) CC genotype were risk factors for PTB progression. Moreover, rs5743867 under addictive (p = 0.005, OR = 1.54, 95% CI: 1.14-2.07) and recessive model (p = 0.004, OR = 1.86, 95% CI: 1.22-2.83) were also risk factors for PTB susceptibility. Our results indicate that polymorphisms in TOLLIP affected the risk of PTB disease.

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Section: Discussionsupporting

confidence: 92%

Evaluation of TLR2,TLR4, and TOLLIP polymorphisms for their role in tuberculosis susceptibility

Huang

Wang

et al. 2018

APMIS

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“…Moreover, associations between the TLR2 genetic diversity and Alzheimer's disease [61] or cognitive function in schizophrenia [62] are highly suggestive of genetically-driven inter-individual ability to modulate neuroinflammatory processes. Of importance is that the TLR2 rs3804099 polymorphism was showed on the one hand to be associated with several inflammatory and infectious diseases including pulmonary tuberculosis, neonatal infection, filariasis, ocular Behcet's disease and cancer [63][64][65][66][67] and to exert a functional impact on the inflammatory response on the other [65,68,69].…”

Section: Discussionmentioning

confidence: 99%

Combined Effect of TLR2 Gene Polymorphism and Early Life Stress On the Age at Onset of Bipolar Disorders

Oliveira

Étain

Lajnef

et al. 2015

European Psychiatry

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Gene-environment interactions may play an important role in modulating the impact of earlylife stressful events on the clinical course of bipolar disorder (BD), particularly associated to early age at onset. Immune dysfunction is thought to be an important mechanism linking childhood trauma with early-onset BD, thus the genetic diversity of immune-related loci may account for an important part of the interindividual susceptibility to this severe subform. Here we investigated the potential interaction between genetic variants of Toll-like receptors 2 (TLR2) and 4 (TLR4), major innate immune response molecules to pathogens, and the childhood trauma questionnaire (CTQ) in age at onset of BD. We recruited 531 BD patients (type I and II or not otherwise specified), genotyped for the TLR2 rs4696480 and rs3804099 and TLR4 rs1927914 and rs11536891 single-nucleotide polymorphisms and recorded for history of childhood trauma using the CTQ. TLR2 and TLR4 risk genotype carrier state and history of childhood emotional, physical and sexual abuses were evaluated in relation to age at onset as defined by the age at first manic or depressive episode. We observed a combined effect of TLR2 rs3804099 TT genotype and reported sexual abuse on determining an earlier age at onset of BD by means of a Kaplan-Meier survival curve (p = 0.002; corrected p = 0.02). Regression analysis, however, was non-significant for the TLR2-CTQ sexual abuse interaction term. The negative effects of childhood sexual abuse on age at onset of BD may be amplified in TLR2 rs3804099 risk genotype carriers through immune-mediated pathways. Clinical characteristics of illness severity, immune phenotypes and history of early life infectious insults should be included in future studies involving large patient cohorts.

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“…Such disease is characterized by cholangitis with remarkable recruiting inflammatory cells in the early stage of infection, followed by hyperplasia of the intrahepatic bile ducts, cholangiofibrosis, and cholelithiasis in the host liver during the chronic stage [4]. Moreover, as a group I carcinogen, C. sinensis can induce human cholangiocarcinoma in chronically infected people [5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Expression of Toll-like receptor (TLR) 2 and TLR4 in the livers of mice infected by Clonorchis sinensis

Yan

et al. 2015

J Infect Dev Ctries

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Introduction: Clonorchis sinensis is one of the most important foodborne pathogens in humans, and can cause biliary diseases such as gallstones, cholecystitis, cholangitis, and cholangiocarcinoma. Toll-like receptors (TLRs) as sensors are crucial to initiating both innate and adaptive immune defenses against pathogens. However, little is known about the hepatic expression of TLRs of hosts induced by C. sinensis infection. Methodology: In the present study, the expression and distribution of TLR2 and TLR4 were investigated in a mouse model of clonorchiasis on days 28, 56, 84, and 112 post-infection (PI) using real-time quantitative reverse transcription polymerase chain reaction (PCR) and immunohistochemically staining, respectively. The levels of cytokines that are mediated by TLR2 and TLR4 were also evaluated using a cytometric bead array. Results: Results showed that the transcripts of TLR2 and TLR4 were upregulated on day 28 PI in C. sinensis-infected mice compared with non-infected ones (p < 0.01). In addition, their proteins were strongly immunohistochemically positive in the cytoplasm and membrane of endothelial cells, fibroblasts, and biliary epithelium cells of C. sinensis-infected mice. The levels of interleukin (IL)-4, IL-10, tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) were increased with activation of TLR2 and TLR4. Conclusions: The expression of TLR2 and TLR4 is upregulated against C. sinensis infection, which suggests that TLR2 and TLR4 might be involved in immune responses during C. sinensis infection.

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Genetic diversity of TLR2, TLR4, and VDR loci and pulmonary tuberculosis in Moroccan patients

Cited by 37 publications

References 63 publications

Evaluation of TLR2,TLR4, and TOLLIP polymorphisms for their role in tuberculosis susceptibility

Evaluation of TLR2,TLR4, and TOLLIP polymorphisms for their role in tuberculosis susceptibility

Combined Effect of TLR2 Gene Polymorphism and Early Life Stress On the Age at Onset of Bipolar Disorders

Expression of Toll-like receptor (TLR) 2 and TLR4 in the livers of mice infected by Clonorchis sinensis

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