Toll-like receptor 7 gene single nucleotide polymorphisms and the risk for systemic lupus erythematosus: a case-control study

Raafat, I; Guindy, Nancy El; Shahin, Rasha Mohamad Hosny; Samy, L A; Refai, Rasha M. El

doi:10.1007/s00393-017-0283-7

Cited by 20 publications

(12 citation statements)

References 17 publications

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“…Among these are TLR7 SNPs, and studies have suspected their potential in progression of different malignancies, and moreover, these SNPs are suggested to predict the response outcome to anti-cancer therapies [25]. In line with these suggestions, the present study examined an intron region of TLR7 gene [26] and enterovirus 71 [27] infections and two autoimmune diseases, systemic lupus erythematosus (SLE) [28,29] and Graves' disease [30]. No clear effect was presented regarding viral infections or Graves' disease, while contradicting results were found in SLE.…”

Section: Discussionmentioning

confidence: 84%

Serum level and single-nucleotide polymorphisms of toll-like receptor-7 among urinary bladder cancer Iraqi patients

Al-Humairi

Al-Musawi

Ad’hiah

2019

Egypt J Med Hum Genet

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Background: Toll-like receptor 7 (TLR7), a member of TLR family, plays a pivotal role in pathogenesis of different malignancies. Among these is urinary bladder cancer (UBC), which has not been extensively studied. Therefore, it was aimed to determine TLR7 serum level in UBC patients and evaluate its association with some demographic and clinicopathological characteristics. In addition, four TLR7 single-nucleotide polymorphisms (SNPs: rs179018, rs179019, rs179020, and rs179021) were investigated to determine their susceptibility role in UBC and inspect SNP's impact on TLR7 level. Sixty-six UBC Iraqi patients were enrolled in this case-control study. Two control samples were also involved, 40 urinary tract infection (UTI) patients, and 48 healthy control subjects. Results: Male gender, older age, and cigarette-smoking are risk factors for UBC. TLR7 level showed a significant decreased median in UBC patients compared to UTI patients or control (1.4 vs. 8.1 and 9.5 ng/ml, respectively; p < 0.001). The decrease was more pronounced in males, age group ≥ 48 years, cigarette-smokers, alcohol non-consumers, clinical stages I-II, and superficial tumor, as well as patients with family history of cancer and untreated patients. Mitomycin C and Bacillus Calmette-Guérin therapies tended to increase TLR7 level. Among the four investigated SNPs, only rs179019 C allele showed significantly uncorrected increased frequency in UBC males compared to control males (p = 0.038), while among UTI females, C allele frequency maintained a significantly corrected decreased frequency compared to control females (p = 0.005). Some SNPs influenced serum level of TLR7, but a significant impact was recorded for rs179019 in UTI females (p = 0.006). Conclusions: Downregulation of TLR7 is suggested to have a role in etiology and pathogenesis of UBC, especially the male, elderly and smoker patients. Mitomycin C and Bacillus Calmette-Guérin may enhance TLR7 production in the blood of UBC patients. TLR7 SNPs are suggested to influence susceptibility to develop UBC, and their potential in impacting TLR7 serum level is augmented.

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Section: Discussionmentioning

confidence: 84%

Serum level and single-nucleotide polymorphisms of toll-like receptor-7 among urinary bladder cancer Iraqi patients

Al-Humairi

Al-Musawi

Ad’hiah

2019

Egypt J Med Hum Genet

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“…The number of SLE patients with current renal involvement was higher in SLE TLR7 hi group, which, might be due to increased anti-DNA and RNA/RNP Abs and, the formation of immune complexes. Two recent studies show an association between TLR7 rs3853839 G risk allele and the development of lupus nephritis or other manifestations of SLE, including malar rash, photosensitivity, pericardial effusion, reduced complement, and anti-dsDNA and anti-Sm auto-Abs (23, 59).…”

Section: Discussionmentioning

confidence: 99%

High TLR7 Expression Drives the Expansion of CD19+CD24hiCD38hi Transitional B Cells and Autoantibody Production in SLE Patients

et al. 2019

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Signaling through Toll-like receptor 7 (TLR7) drives the production of type I IFN and promotes the activation of autoreactive B cells and is implicated in the pathogenesis of systemic lupus erythematosus (SLE). While TLR7 has been extensively studied in murine lupus, much less is known about its role in the pathogenesis of human SLE. Genetic studies support a link between the TLR7 rs3853839 C/G polymorphism, which affects TLR7 mRNA turnover, and SLE susceptibility; however, the effects of this polymorphism on B cells have not been studied. Here we determined how changes in TLR7 expression affect peripheral B cells and auto-Ab production in SLE patients. High TLR7 expression in SLE patients driven by TLR7 rs3853839 C/G polymorphism was associated with more active disease and upregulation of IFN-responsive genes. TLR7 hi SLE patients showed an increase in peripheral B cells. Most notably, the percentage and numbers of CD19 + CD24 ++ CD38 ++ newly-formed transitional (TR) B cells were increased in TLR7 hi SLE patients as compared to HCs and TLR7 norm/lo SLE patients. Using auto-Ab arrays, we found an increase and enrichment of auto-Ab specificities in the TLR7 hi SLE group, including the production of anti-RNA/RNP-Abs. Upon in vitro TLR7 ligand stimulation, TR B cells isolated from TLR7 hi but not TLR7 norm/lo SLE patients produced anti-nuclear auto-Abs (ANA). Exposure of TR B cells isolated from cord blood to IFNα induced the expression of TLR7 and enabled their activation in response to TLR7 ligation in vitro . Our study shows that overexpression of TLR7 in SLE patients drives the expansion of TR B cells. High TLR7 signaling in TR B cells promotes auto-Ab production, supporting a possible pathogenic role of TR B cells in human SLE.

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“…However, TLR7 may be an interesting gene for future studies given that an additional moderately associated SNP was found in this gene. Other SNPs in this gene have been linked to the antibody‐mediated autoimmune diseases, systemic lupus erythematosus (SLE) (Kawasaki et al , ; Enevold et al , ; Wang et al , ; Raafat et al , ) and Graves disease (Xiao et al , ). Moreover, this gene shows copy number variation (CNV) that has been linked to SLE (Garcia‐Ortiz et al , ; Pacheco et al , ) and Behçet Disease (Fang et al , ).…”

Section: Discussionmentioning

confidence: 99%

Identification of genetic biomarkers for alloimmunization in sickle cell disease

et al. 2019

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Summary Most sickle cell disease (SCD) patients rely on blood transfusion as their main treatment strategy. However, frequent blood transfusion poses the risk of alloimmunization. On average, 30% of SCD patients will alloimmunize while other patient groups form antibodies less frequently. Identification of genetic markers may help to predict which patients are at risk to form alloantibodies. The aim of this study was to evaluate whether genetic variations in the Toll‐like receptor pathway or in genes previously associated with antibody‐mediated conditions are associated with red blood cell (RBC) alloimmunization in a cohort of SCD patients. In this case‐control study, cases had a documented history of alloimmunization while controls had received ≥20 RBC units without alloantibody formation. We used a customized single nucleotide polymorphism (SNP) panel to genotype 690 SNPs in 275 (130 controls, 145 cases) patients. Frequencies were compared using multiple logistic regression analysis. In our primary analysis, no SNPs were found to be significantly associated with alloimmunization after correction for multiple testing. However, in a secondary analysis with a less stringent threshold for significance we found 19 moderately associated SNPs. Among others, SNPs in TLR1/TANK and MALT1 were associated with a higher alloimmunization risk, while SNPs in STAM/IFNAR1 and STAT4 conferred a lower alloimmunization risk.

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Toll-like receptor 7 gene single nucleotide polymorphisms and the risk for systemic lupus erythematosus: a case-control study

Cited by 20 publications

References 17 publications

Serum level and single-nucleotide polymorphisms of toll-like receptor-7 among urinary bladder cancer Iraqi patients

Serum level and single-nucleotide polymorphisms of toll-like receptor-7 among urinary bladder cancer Iraqi patients

High TLR7 Expression Drives the Expansion of CD19+CD24hiCD38hi Transitional B Cells and Autoantibody Production in SLE Patients

Identification of genetic biomarkers for alloimmunization in sickle cell disease

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