<i>MicroRNA-146a</i>and<i>Ets-1</i>gene polymorphisms in ocular Behçet's disease and Vogt–Koyanagi–Harada syndrome

Zhou, Qingyun; Hou, Shengping; Liang, Liang; Li, Xinyu; Tan, Xiaoyu; Lin, Wei; Lei, Bo; Kijlstra, Aize; Yang, Peizeng

doi:10.1136/annrheumdis-2012-201627

Cited by 79 publications

(64 citation statements)

References 37 publications

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“…This form of miRNA dysregulation was demonstrated in Han Chinese BD patients in miR146a/rs2910164, miR-196a2/rs11614913, and miR-182/ rs76481776 (Table 3). In the first study, BD was associated with variant rs2910164 within miR-146a, a key regulator of the type I interferon pathway [62,63]. Healthy individuals with the homozygous risk allele for miR-146a/rs2910164 had increased miR-146a expression and increased serum levels of pro-inflammatory cytokines IL-1β, IL-17, and tumor necrosis factor alpha (TNF-α).…”

Section: Behçet's Diseasementioning

confidence: 98%

Epigenetics and Vasculitis: a Comprehensive Review

Renauer

Coit

Sawalha

2015

Clinic Rev Allerg Immunol

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Vasculitides represent a group of relatively rare systemic inflammatory diseases of the blood vessels. Despite recent progress in understanding the genetic basis and the underlying pathogenic mechanisms in vasculitis, the etiology and pathogenesis of vasculitis remain incompletely understood. Epigenetic dysregulation plays an important role in immune-mediated diseases, and the contribution of epigenetic aberrancies in vasculitis is increasingly being recognized. Histone modifications in the PR3 and MPO gene loci might be mechanistically involved in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis. Similarly, other studies revealed important epigenetic contribution to other vasculitides, including Kawasaki disease and IgA vasculitis. More recently, genome-wide epigenomic studies have been performed in several vasculitides. A recent genome-wide DNA methylation study uncovered an important role for epigenetic remodeling of cytoskeleton-related genes in the pathogenesis of Behçet's disease and suggested that reversal of some of these DNA methylation changes associates with disease remission. Genome-wide DNA methylation profiling characterized the inflammatory response in temporal artery tissue from patients with giant cell arteritis and showed increased activation of calcineurin/nuclear factor of activated T cells (NFAT) signaling, prompting the suggestion that a specific calcineurin/NFAT inhibitor that is well tolerated and with the added beneficial anti-platelet activity, such as dipyridamole, might be of therapeutic potential in giant cell arteritis. While epigenetic studies in systemic vasculitis are still in their infancy, currently available data clearly indicate that investigating the epigenetic mechanisms underlying these diseases will help to better understand the pathogenesis of vasculitis and provide novel targets for the development of disease biomarkers and new therapies.

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Section: Behçet's Diseasementioning

confidence: 98%

Epigenetics and Vasculitis: a Comprehensive Review

Renauer

Coit

Sawalha

2015

Clinic Rev Allerg Immunol

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“…Li et al demonstrated that ApoE regulates the expression of miR-146a in monocytes and macrophages to repress NF-B signaling in these cells, and intravascular delivery of miR-146a mimetics can inhibit atherogenesis in mouse models 13) . However, the 4 gene polymorphism causes strong dysfunction of ApoE, which suppresses the level of miR146a 13,38,50) . Based on the finding that ApoE 4 induced decreasing expression of miR-146a in ACI patients, we suggest that the downregulation of NF-B-dependent pathways by miR-146a through a critical negative feedback regulatory loop was attenuated by the effects of ApoE 4.…”

Section: The Influence Of Apoe 4 On Mir-146a Expression In Aci Patientsmentioning

confidence: 99%

“…In our study, two functional SNPs in miR-146a were chosen to evaluate the association between miR-146a polymorphisms and ACI risk. The two SNPs in miRNA-146a, rs2910164 and rs57095329, have been reported to influence the expression level of mature miR-146a; thus, these SNPs may ultimately affect an individual's susceptibility to disease 10,37,38) . Our results revealed that the rs2910164 polymorphism was associated with an increased risk of ACI; the C allele of rs2910164 was more frequent in patients with ACI compared with the G allele, indicating that the C allele of rs2910164 is associated with an increased risk of ACI susceptibility.…”

Section: The Influence Of Apoe 4 On Mir-146a Expression In Aci Patientsmentioning

confidence: 99%

Apolipoprotein E Epsilon 4 Enhances the Association between the rs2910164 Polymorphism of miR-146a and Risk of Atherosclerotic Cerebral Infarction

Zhong

Cai

Cheng

et al. 2016

J Atheroscler Thromb

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Aim: To analyse the relationship between two potentially functional single-nucleotide polymorphisms (SNPs) of the miR-146a gene (rs2910164 and rs57095329) and the risk of atherosclerotic cerebral infarction (ACI).Methods: A total of 297 patients with ACI and 300 matched healthy individuals were enrolled in the study. The miR-146a polymorphism was detected using the polymerase chain reaction -restriction fragment length polymorphism method. Results: A significant difference in the C allele frequency at rs2910164 (p 0.028) was noted between patients with ACI and control subjects. In contrast, the genotype and allele frequencies of rs57095329 were not statistically associated with ACI. In addition, the decreased expression of miR146a was significantly more frequent in ACI patients who were ApoE 4 ( ) carriers (p 0.0233), and rs2910164 G C was intimately associated with the ApoE 4-containing genotype in patients compared with the ApoE 4 ( ) carriers (p 0.0323). Conclusions: Our findings indicated that the C allele of rs2910164 miR-146a is an important risk factor for ACI, and ApoE 4 may function through attenuating miR-146a expression to enhance ACI susceptibility. This study provides new information about the possible relationship between miR146a and ApoE 4 in the development of ACI, with potentially important therapeutic implications.

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“…[15][16][17] Many studies [18][19][20][21][22][23] have demonstrated that miRNAs play a role in pathogenesis of human autoimmune and autoinflammatory diseases such as Behcet's disease (BD) and AS. Earlier studies 22 have shown that the miR-146a rs2910164 CC genotype and C allele confer risk for BD. Having more than two gene copies of miR-23a, miR146a, and miR-301a has been shown to be linked to the susceptibility to Vogt-Koyanagi-Harada (VKH) syndrome.…”

Section: Discussionmentioning

confidence: 99%

miRNA Copy Number Variants Confer Susceptibility to Acute Anterior Uveitis With or Without Ankylosing Spondylitis

Yang

Yue

et al. 2017

Invest. Ophthalmol. Vis. Sci.

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MicroRNA-146aandEts-1gene polymorphisms in ocular Behçet's disease and Vogt–Koyanagi–Harada syndrome

Abstract: Our study identified a strong association of rs2910164 of miR-146a with BD in a Chinese population and decreased expression of miR-146a and certain proinflammatory cytokines in individuals carrying the CC genotype.

Cited by 79 publications

References 37 publications

Epigenetics and Vasculitis: a Comprehensive Review

Epigenetics and Vasculitis: a Comprehensive Review

Apolipoprotein E Epsilon 4 Enhances the Association between the rs2910164 Polymorphism of miR-146a and Risk of Atherosclerotic Cerebral Infarction

miRNA Copy Number Variants Confer Susceptibility to Acute Anterior Uveitis With or Without Ankylosing Spondylitis

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