The association between toll-like receptor 4 polymorphisms and diabetic retinopathy in Chinese patients with type 2 diabetes

Xu, Yuxin; Jiang, Zhengxuan; Huang, Jinhai; Quanfei, Meng; Coh, Paul; Tao, Liming

doi:10.1136/bjophthalmol-2015-306677

Cited by 28 publications

(19 citation statements)

References 34 publications

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“…However, our data did not show a significant association between TLR2 SNPs and PTDM. Xu et al [36] and Sun et al [26] recognized that TLR4 rs1927914 and TLR6 rs3775073 SNPs have a significant relationship with T2DM, and our data also revealed that those SNPs are associated with PTDM.…”

Section: Discussionsupporting

confidence: 68%

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Significant Association between Toll-Like Receptor Gene Polymorphisms and Posttransplantation Diabetes Mellitus

Kim

Kim²,

Park³

et al. 2016

Nephron

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Background: Posttransplantation diabetes mellitus (PTDM) is an important metabolic complication after renal transplantation. Activation of the innate immune system via toll-like receptors (TLRs) is implicated in the pathogenesis of insulin resistance and deficiency. Although links between diabetes, dysregulated innate immune responses, and the TLR signaling pathway have been reported, no study so far has investigated their associations with PTDM. In this study, we ascertained whether single nucleotide polymorphisms (SNPs) in TLRs are associated with PTDM in the Korea population. Methods: A total of 305 patients who received renal transplants without previously diagnosed diabetes were included. We analyzed the association between PTDM development and 6 SNPs within 2 genes of TLR2, 1 gene of TLR4, and 3 genes of TRL6. Results: Of 305 patients, PTDM developed in 51 patients (16.6%). Patients in the PTDM group were older than those in the non-PTDM group (45.56 ± 1.28 vs. 38.28 ± 0.71 years). Patients with PTDM had significantly higher allele frequency compared to those without PTDM for the TLR4 rs1927914*T, TLR6 rs3775073*A, TLR6 rs3821985*C, and TLR6 rs1039559*C alleles. Of the 6 SNPs, rs1927914 in the TLR4 gene and rs1039559 in the TLR6 gene were significantly associated with the development of PTDM after adjustment for age, gender, and tacrolimus usage. Conclusions: Our study demonstrates a significant association between SNPs rs1927914 in TLR4 and rs1039559 in TLR6 and PTDM in the renal transplantation recipient group. These data suggest that the activation of the innate immune system and inflammation via TLR activation might have an essential role in the pathogenesis of PTDM in renal transplantation.

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Section: Discussionsupporting

confidence: 68%

“…Gene polymorphisms in TLRs affect the innate immune response [25]. Previous studies have recognized that polymorphisms in TLRs are associated with the development of diabetes [14,26,27,28,29,30,31,32,33,34,35,36]. Table 5 shows polymorphisms previously associated with diabetes and references.…”

Section: Discussionmentioning

confidence: 99%

Significant Association between Toll-Like Receptor Gene Polymorphisms and Posttransplantation Diabetes Mellitus

Kim

Kim²,

Park³

et al. 2016

Nephron

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“…Any deregulation of TLR4 signaling due to single nucleotide polymorphisms (SNPs) in the extracellular domain of TLR4 may alter the ligand binding capacity and hence disturb the balance of pro- and anti-inflammatory cytokines [81]. It has been reported that rs4986790, rs4986791, rs10759931 and rs1927914 in TLR4 positively modulate the risk of DR [3, 81, 136]. …”

Section: The Other Polymorphisms Modulating Risk Of Drmentioning

confidence: 99%

Candidate gene studies of diabetic retinopathy in human

2016

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Diabetic retinopathy (DR) is a multifactorial disease with complex pathophysiology. It is the main cause of blindness among the people in productive age. The purpose of this literature review is to highlight recent achievements in the genetics of diabetic retinopathy with particular focus on candidate gene studies. We summarized most of the available published data about candidate genes for diabetic retinopathy with the goal to identify main genetic aspects. We conclude that genetic studies reported contradictory findings and no genetic variants meet criteria of a diagnostic marker, or significantly elucidate the root of DR development. Based on these findings it is important to continue with the research in the field of DR genetics, mainly due to the fact that currently new possibilities and approaches associated with utilization of next-generation sequencing are available.

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“…Toll-like receptors (TLRs) are a family of receptors that are associated with pathogen invasion and are involved in the innate immune response (8). Activation of the TLRs triggers downstream signals resulting in the secretion of cytokines and chemokines, and inflammatory response initiation (9,10). A previous review has concluded that TLR is involved in the induction and maintenance of chronic pain via initiation of central immune signaling (11).…”

Section: Introductionmentioning

confidence: 99%

Sparstolonin B selectively suppresses toll‑like receptor‑2 and ‑4 to alleviate neuropathic pain

Jin

Zhou

2017

Mol Med Report

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It has been previously demonstrated that sparstolonin B (SsnB) inhibits toll‑like receptor (TLR)‑2 and TLR‑4. The present study investigated the effect of SsnB on neuropathic pain (NP). A chronic constriction injury (CCI) model was constructed in rats and the protein expression of TLR‑2 and TLR‑4 was determined by western blot analysis. Rats were divided into the following three groups: Rats with sham surgery (control group); rats with CCI (model group); and rats with CCI and injection of SsnB (SsnB group). The mechanical withdrawal threshold (MWT) was measured by using Von Frey filaments. In addition, the mRNA and protein expression levels of nuclear factor‑κB (NF‑κB) were investigated by reverse transcription‑quantitative polymerase chain reaction and western blot analysis, respectively, and the concentrations of tumor necrosis factor‑α (TNF‑α) and interleukin (IL)‑6 were determined by ELISA. Compared with control rats, the protein expression levels of TLR‑2 and TLR‑4 were increased in model rats (P<0.001). At 7 and 14 days after surgery, the MWTs in the model group were significantly reduced compared with the control group (P<0.001). However, the MWTs in the SsnB group were significantly increased compared with the model group (P<0.001). The results also demonstrated that the mRNA and protein expression levels of NF‑κB, and the protein expression levels of TNF‑α and IL‑6, were increased in model group compared with the control group (P<0.001). Furthermore, these increases in expression were all reduced in the SsnB group compared with the model group. Therefore, the results indicate that SsnB may alleviate NP via suppression of TLR‑2 and TLR‑4, and may be a potential drug for the treatment of NP.

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The association between toll-like receptor 4 polymorphisms and diabetic retinopathy in Chinese patients with type 2 diabetes

Abstract: This study suggested that rs1927914 and rs1927911 were associated with type 2 diabetes mellitus and that rs1927914 was associated with susceptibility to DR in a Han Chinese population.

Cited by 28 publications

References 34 publications

Significant Association between Toll-Like Receptor Gene Polymorphisms and Posttransplantation Diabetes Mellitus

Significant Association between Toll-Like Receptor Gene Polymorphisms and Posttransplantation Diabetes Mellitus

Candidate gene studies of diabetic retinopathy in human

Sparstolonin B selectively suppresses toll‑like receptor‑2 and ‑4 to alleviate neuropathic pain

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