Toll-like receptor 9 polymorphisms in brazilian patients with systemic lupus erythematosus: a pilot study

Toll-like receptor 9 (TLR9) is an important component of the innate immune system and have been associated with several autoimmune diseases, such as Systemic Lupus Erythematosus (SLE). The aim of this study was to investigate polymorphisms in TLR9 gene in a Brazilian SLE patients group and their association with clinical manifestation, particularly Jaccoud’s arthropathy (JA). We analyzed DNA samples from 204 SLE patients, having a subgroup of them presenting JA (n=24). A control group (n=133) from the same city was also included. TLR9 single nucleotide polymorphisms (SNPs) (−1237 C>T and +2848 G>A) were identified by sequencing analysis. The TLR9 gene genotype frequency was similar both in SLE patients and the control group. In the whole SLE population, an association between the homozygosis of allele C at position −1237 with psychosis and anemia (p < 0.01) was found. Likewise, the homozygosis of allele G at position +2848 was associated with a discoid rash (p < 0.05). There was no association between JA and TLR9 polymorphisms. These data show that TLR9 polymorphisms do not seem to be a predisposing factor for SLE in the Brazilian population, and that SNPs are not associated with JA.

Ovine Toll-like Receptor 9 (TLR9) Gene Variation and Its Association with Flystrike Susceptibility

Toll-like receptors (TLRs) are a family of proteins that play a role in innate immune responses by recognising pathogen-associated molecular patterns derived from various microbes. Of these receptors, TLR9 recognises bacterial and viral DNA containing unmethylated cytosine-phosphate-guanine (CpG) motifs, and variation in TLR9 has been associated with resistance to various infectious diseases. Flystrike is a problem affecting the sheep industry globally and the immune response of the sheep has been suggested as one factor that influences the response to the disease. In this study, variation in ovine TLR9 from 178 sheep with flystrike and 134 sheep without flystrike was investigated using a polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) approach. These sheep were collected from both commercial and stud farms throughout New Zealand and they were of 13 different breeds, cross-breds and composites. Four alleles of TLR9 were detected, including three previously identified alleles (*01, *02 and *03) and a new allele (*04). In total six single nucleotide polymorphisms (SNPs) were found. Of the three common alleles in the sheep studied, the presence of *03 was found to be associated with a reduced likelihood of flystrike being present (OR = 0.499, p = 0.024). This suggests that variation in ovine TLR9 may affect a sheep’s response to flystrike, and thus the gene may have value as a genetic marker for improving resistance to the disease.

Association of TLR 9 gene polymorphisms with remission in patients with rheumatoid arthritis receiving TNF-α inhibitors and development of machine learning models

Toll-like receptor (TLR)-4 and TLR9 are known to play important roles in the immune system, and several studies have shown their association with the development of rheumatoid arthritis (RA) and regulation of tumor necrosis factor alpha (TNF-α). However, studies that investigate the association between TLR4 or TLR9 gene polymorphisms and remission of the disease in RA patients taking TNF-α inhibitors have yet to be conducted. In this context, this study was designed to investigate the effects of polymorphisms in TLR4 and TLR9 on response to TNF-α inhibitors and to train various models using machine learning approaches to predict remission. A total of six single nucleotide polymorphisms (SNPs) were investigated. Logistic regression analysis was used to investigate the association between genetic polymorphisms and response to treatment. Various machine learning methods were utilized for prediction of remission. After adjusting for covariates, the rate of remission of T-allele carriers of TLR9 rs352139 was about 5 times that of the CC-genotype carriers (95% confidence interval (CI) 1.325–19.231, p = 0.018). Among machine learning algorithms, multivariate logistic regression and elastic net showed the best prediction with the area under the receiver-operating curve (AUROC) value of 0.71 (95% CI 0.597–0.823 for both models). This study showed an association between a TLR9 polymorphism (rs352139) and treatment response in RA patients receiving TNF-α inhibitors. Moreover, this study utilized various machine learning methods for prediction, among which the elastic net provided the best model for remission prediction.

First Survey of SNPs in TMEM154, TLR9, MYD88 and CCR5 Genes in Sheep Reared in Italy and their Association with Resistance to SRLVs Infection

Maedi-visna virus (MVV) and caprine arthritis encephalitis virus (CAEV), referred to as small ruminant lentiviruses (SRLVs), belong to the genus Lentivirus of the Retroviridae family. SRLVs infect both sheep and goats, causing significant economic losses and animal welfare damage. Recent findings suggest an association between serological status and allelic variants of different genes such as TMEM154, TLR9, MYD88 and CCR5. The aim of this work was to investigate the role of specific polymorphisms of these genes in SRLVs infection in some sheep flocks in Italy. In addition to those already known, novel variants in the TMEM154 (P7H, I74V, I105V) gene were detected in this study. The risk of infection was determined finding an association between the serological status and polymorphisms P7H, E35K, N70I, I74V, I105V of TMEM154, R447Q, A462S and G520R in TLR9 gene, H176H* and K190K* in MYD88 genes, while no statistical association was observed for the 4-bp deletion of the CCR5 gene. Since no vaccines or treatments have been developed, a genetically based approach could be an innovative strategy to prevent and to control SRLVs infection. Our findings are an important starting point in order to define the genetic resistance profile towards SRLVs infection.

The Association of TLR2, TLR3, and TLR9 Gene Polymorphisms With Susceptibility to Talaromycosis Among Han Chinese AIDS Patients in Guangdong

BackgroundTalaromycosis (TM) caused by Talaromyces marneffei (T. marneffei) is a growing public health concern. Although Toll-like receptor (TLR) genes play a critical role in the host defense against fungal infection, the influence of polymorphisms in these genes on the susceptibility of acquired immune deficiency syndrome (AIDS) patients to TM remains unknown. This study aims to uncover the associations of single nucleotide polymorphisms (SNPs) in TLR genes with TM susceptibility among patients with AIDS.MethodsAltogether 200 AIDS patients complicated with TM, 200 matched AIDS patients without TM, and 76 healthy controls (HCs) were enrolled in this case-control study. In total, 23 SNPs in the TLR2, TLR4, and TLR9 genes, which may influence the susceptibility of AIDS patients to TM, were checked by the time of flight mass spectrometry (TOF/MS) method among these Han Chinese subjects.ResultsNo significant differences in genotype or allele frequencies of selected SNPs were found among the TM group, Non-TM group, and HC group. Haplotype analysis also demonstrated no correlation of these SNPs with TM. However, subgroup analysis showed that the genotype TT and the T allele in TLR2 SNP rs1339 were more frequent in typical TM cases than controls (50.0 vs. 35.8%, 70.5 vs. 59.7%); the frequency of the GT genotype in TLR2 SNP rs7656411 was markedly higher in severe TM cases compared to controls (57.8 vs. 34.4%).ConclusionOur results demonstrate a genetic connection of TLR2 SNPs rs1339 and rs7656411 with an increased susceptibility and severity of TM among Han Chinese populations.

Genetic variants of TLR9 Gene and Chronic Kidney Disease Susceptibility

Objectives Chronic kidney disease (CKD) is a common condition that can lead to renal dysfunction and is closely in relation to an increased cardiovascular risk and mortality risk. CKD is an important public health issue, and recent genetic studies have verified common CKD susceptibility variants. In this research, we examined the interrelationship between candidate genes polymorphisms of IFNL induction and signaling pathway and CKD. Methods 92 CKD patients and 330 healthy subjects as control were participated in this research. Replication set consisting 137 CKD with CGN patients and 446 controls was used for additional analysis. The genotype of SNPs was determined by the Axiom Genome-Wide Human Assay and SNaPshot assay. Results The SNPs of IFNL3 and IFNL2 were significantly associated with chronic kidney disease in the codominant (p = 0.015, p = 0.013, respectively). The SNP of IFNRA2 was significantly associated with chronic kidney disease in the codominant (p = 0.029). The SNP of TLR9 was significantly associated with chronic kidney disease in the codominant (p = 0.016), dominant (p = 0.047) and recessive (p = 0.049). The SNP of IL-22 was significantly associated with chronic kidney disease in the codominant (p = 0.049). No significant associations involving IFNL3, IFNL2 and IL22 were observed in the replication set whereas concerning the rs187084, in the TLR9 gene, a significant association was observed pooling the original and the replication sets. Conclusions This results shows a possibility that IFNL induction and signal pathway genes polymorphisms as a risk factor for CKD. Secondly, our results seem to TRL9 gene variant may be play a risk factor on CKD with CGN.

Toll-Like Receptor 9 (TLR9) Gene C/T (rs352140) Polymorphisms in Adult Primary Immune Thrombocytopenia

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet count and increased bleeding risk. The initial event(s) leading to antiplatelet autoimmunity remains unclear. Toll-like receptors (TLRs) are the most well-characterized pattern recognition receptors and are a transmembrane protein coded by the Toll genes family. In addition to their protective role in immunity, it is also becoming clear that TLRs exhibit homeostatic roles. Toll-like receptors play potential roles in the development of disease and its maintenance. The objective of this study is to evaluate the distribution of TLR9 gene C/T (rs352140) polymorphisms and its possible association with clinicopathological finding in Egyptian adult primary ITP. This study was carried out at Internal Medicine Department, Menoufia University Hospital, Egypt, from August 2018 to January 2020. Eighty adults (≥ 18 years) were enrolled in the study; 40 patients with primary ITP and 40 healthy individuals as controls. Identification of the TLR9 C/T (rs352140) polymorphic variant was performed by polymerase chain reaction–restriction fragment length polymorphism. In our study, we excluded any other causes of secondary ITP. Distribution of the TLR9 C/T genotypes did not exhibit significant deviation between patients and controls. There was no significant difference between studied groups as regards allele (C and T) frequency. There was no significant difference regarding TLR9 gene C/T (rs352140) polymorphisms between Egyptian adult with primary ITP and controls. TLR9 gene C/T (rs352140) polymorphisms have no relation to any of the clinicohematological variables in primary ITP in Egyptians.