Dataset Information

The LMP2 CfoI polymorphism is associated with ankylosing spondylitis (AS) risk but not with acute anterior uveitis (AAU): A meta-analysis.

ABSTRACT: BACKGROUND:Ankylosing spondylitis (AS) is one of the most common chronic inflammatory disorders affecting the sacroiliac joints, spine, and peripheral joints. Apart from HLA-B27, the LMP2 gene has been shown to play a role in the pathogenesis of AS as well as AAU in AS. However, genetic associations between LMP2 CfoI polymorphism and AS and AAU were inconclusive. We aimed to investigate the correlation of LMP2 CfoI polymorphism and AS and AAU using meta-analysis. METHODS:An exhaustive search was conducted using the PubMed, Embase, Cochrane Library, and Chinese National Knowledge Infrastructure (CNKI) electronic databases. The strength association was assessed by crude ORs with 95% CI. RESULTS:Eight eligible records with 449 AS patients and 317 healthy controls were included in the present study. The allelic model of the LMP2 CfoI polymorphism is associated with AS risk (OR?=?0.60, 95%CI?=?[0.32, 1.11], P?=?.003). A stratified analysis based on ethnicity has shown that the allelic model of LMP2 CfoI was associated with AS in the Caucasian population (OR?=?0.72, 95%CI?=?[0.55, 0.93], P?=?.01) but not in the Asian population (P?>?.05). Furthermore, no association was detected between LMP2 CfoI polymorphism and AS complication (AAU). CONCLUSION:Our combined results revealed that the allelic model of LMP2 CfoI might be a protective factor for AS in the Caucasian population. Nevertheless, future studies on different ethnicities with larger sample sizes are needed to obtain a more convincing result.

SUBMITTER: Qian Y

PROVIDER: S-EPMC6855618 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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The LMP2 CfoI polymorphism is associated with ankylosing spondylitis (AS) risk but not with acute anterior uveitis (AAU): A meta-analysis.

Qian Yufeng Y Chen Bingqian B Sheng Xiaowen X Peng Yuqin Y

Medicine 20191101 45

<h4>Background</h4>Ankylosing spondylitis (AS) is one of the most common chronic inflammatory disorders affecting the sacroiliac joints, spine, and peripheral joints. Apart from HLA-B27, the LMP2 gene has been shown to play a role in the pathogenesis of AS as well as AAU in AS. However, genetic associations between LMP2 CfoI polymorphism and AS and AAU were inconclusive. We aimed to investigate the correlation of LMP2 CfoI polymorphism and AS and AAU using meta-analysis.<h4>Methods</h4>An exhaus ...[more]

PMID: 31702633

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Project description:<p><strong>BACKGROUND: </strong>It has been reported that the gut microbiome is involved in the pathogenesis of uveitis, but the specific pathogenic microbes and metabolites in different types of uveitis are still unclear.</p><p><strong style='color: rgb(54, 54, 54);'>METHODS</strong><strong>: </strong>Microbiome and metabolites were detected using 16S ribosomal DNA and LC‒MS/MS (liquid chromatography tandem mass spectrometry) in 45 individuals, including 16 patients with Vogt Koyanagi Harada (VKH), 11 patients with acute anterior uveitis (AAU) and 18 healthy controls.</p><p><strong style='color: rgb(54, 54, 54);'>RESULT:</strong> The diversity of intestinal microbes among the VKH, AAU and control groups was not significantly different. 13 specific microbes and 38 metabolites were detected in the VKH group, and 7 metabolites (vanillin, erythro-isoleucine, pyrimidine, 1-aminocyclopropanecarboxylic acid, beta-tocopherol, (-)-gallocatechin and N1-methyl-4-pyridone-3-carboxamide) significantly changed only in patients with VKH, which mainly acted on nicotinamide and nicotinamide metabolism and biotin metabolism (p<0.05). Compared with the VKH group, the AAU group had milder intestinal changes. Only 11 specific microbes and 29 metabolites changed in the AAU group, while these metabolites were not specific (p<0.05). These metabolites mainly acted on arachidonic acid metabolism. In addition, 3 microbes and 2 metabolites had the same changes in the VKH and AAU groups (p<0.05). Multiple correlations were found between gut microbes and metabolites in the VKH and AAU groups. 6 microbes (Pediococcus, Pseudomonas, Rhodococcus, Photobacterium, Gardnerella and Lawsonia) and 2 metabolites (pyrimidine and gallocatechin) as biomarkers could effectively distinguish patients with VKH from patients with AAU and healthy individuals, with AUC (area under the curve) values greater than 82%. 4 microbes (Lentilactobacillus, Lachnospiraceae_UCG-010, Cetobacterium, Liquorilactobacillus) could distinguish patients with AAU from patients with VKH and healthy controls with AUC>76%.</p><p><strong style='color: rgb(54, 54, 54);'>CONCLUSION: </strong>Significant differences in intestinal microbes and metabolites suggest their different roles in the pathogenesis of uveitis entities. Changes in the metabolism of certain B vitamins may be involved in the pathogenesis of VKH.</p>

Project description:BACKGROUND:Anterior uveitis is the most common extra-articular manifestation of ankylosing spondylitis (AS). AS-related anterior uveitis frequently presents as acute, recurrent iridocyclitis; therefore, AS is often initially suspected by an ophthalmologist, not by a rheumatologist. In this study, we aimed to investigate the relationship between the recurrence of anterior uveitis and the subsequent incidence of AS. METHODS:From a national sample cohort, 10,483 patients with new-onset uveitis between 2004 and 2013 and 52415 matched control subjects who had never experienced uveitis were selected. Among the patients with new-onset uveitis, a subpopulation of patients with recurrent uveitis, defined as a minimum 120-day reported interval between consecutive claims of uveitis (based on diagnostic codes) treated with local or systemic steroids or immune-modulating drugs, was identified. The incidence rates of AS were calculated according to the number of episodes of uveitis, and the incidence rate ratios (IRRs) were derived on the basis of the incidence rate in the control group. RESULTS:The incidence rate per 100,000 person-years of AS after the first uveitis episode was 121.5, whereas the incidence in the control group was 16.9 (IRR, 7.40; 95% CI, 4.99-10.98); after the second uveitis episode, the IRR increased to 17.71 (95% CI, 10.44-30.06). In male and female patients with recurrent uveitis, the incidence rates of AS were 284.1 and 268.7 per 100,000 person-years, respectively. In patients aged under 40 years, the IRR of the recurrent uveitis group was 46.78 (95% CI, 19.61-111.61). In patients aged over 59 years, AS incidence in the recurrent uveitis group did not differ from that in the control group. CONCLUSIONS:The risk of subsequent AS increased with the number of episodes of anterior uveitis. This quantitative evidence could contribute to the establishment of a rationale for ancillary workup for possible systemic associations in patients with recurrent uveitis.

Project description:BackgroundAnkylosing spondylitis (AS) is a chronic inflammatory disease. Excess cardiovascular risks were well recognized in patients with AS and were attributed to prolonged systemic inflammation. Uveitis is one of the most common extra-articular symptoms of AS and is also considered an indicator of systemic inflammation. This study aimed to investigate whether uveitis was a risk factor for developing acute myocardial infarction (AMI) in patients with AS using the National Health Insurance Research Database (NHIRD).MethodsData were collected from the NHIRD over a fifteen-year period. Variables were analyzed using the Pearson chi-square test and Fisher's exact test. Risk factors for the occurrence of AMI were examined by calculating hazard ratio. Kaplan-Meier analysis was performed to compare the cumulative incidence of AMI in the uveitis and non-uveitis cohorts.ResultsA total of 5905 patients with AS were enrolled, including 1181 patients with uveitis (20%) and 4724 patients without uveitis (80%). The Kaplan-Meier method with the log-rank test showed that the uveitis group had a significantly higher cumulative hazard for patients with AMI than the non-uveitis group (p < 0.001). The adjusted hazard ratio (aHR) of AMI was higher in the uveitis group than in the non-uveitis group (aHR = 1.653, p < 0.001). Stratified analysis revealed that patients with uveitis had an increased risk of developing AMI regardless of their sex (male/female aHR = 1.688/1.608, p < 0.001). Patients with uveitis in all age groups were independently associated with an increased risk of developing AMI compared to those without uveitis (20-39 years/40-59 years/≥ 60 years, aHR = 1.550, 1.579, 3.240, p < 0.001). Patients with uveitis had a higher probability of developing AMI regardless of comorbidities. Uveitis patients with comorbidities had a higher risk of developing AMI compared to uveitis patients without comorbidities.ConclusionUveitis is a significant risk factor for developing AMI in patients with AS. Physicians should be aware of the potential cardiovascular risk in AS patients with uveitis, especially simultaneously with other traditional risk factors of AMI. Further prospective studies are needed to elucidate the underlying mechanism between uveitis and AMI in patients with AS.

Project description:ObjectiveTo investigate the functional consequences of the single-nucleotide polymorphism rs4648889 in a putative enhancer upstream of the RUNX3 promoter associated with susceptibility to ankylosing spondylitis (AS).MethodsUsing nuclear extracts from Jurkat cells and primary human CD8+ T cells, the effects of rs4648889 on allele-specific transcription factor (TF) binding were investigated by DNA pull-down assay and quantitative mass spectrometry (qMS), with validation by electrophoretic mobility shift assay (EMSA), Western blotting of the pulled-down eluates, and chromatin immunoprecipitation (ChIP)-quantitative polymerase chain reaction (qPCR) analysis. Further functional effects were tested by small interfering RNA knockdown of the gene for interferon regulatory factor 5 (IRF5), followed by reverse transcription-qPCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) to measure the levels of IFNγ messenger RNA (mRNA) and protein, respectively.ResultsIn nuclear extracts from CD8+ T cells, results of qMS showed that relative TF binding to the AS-risk A allele of rs4648889 was increased 3.7-fold (P < 0.03) for Ikaros family zinc-finger protein 3 (IKZF3; Aiolos) and components of the NuRD complex, including chromodomain helicase DNA binding protein 4 (CHD4) (3.6-fold increase; P < 0.05) and retinoblastoma binding protein 4 (RBBP4) (4.1-fold increase; P < 0.03). In contrast, IRF5 bound significantly more to the AS-protective G allele compared to the AS-risk A allele (fold change 8.2; P = 0.003). Validation with Western blotting, EMSA, and ChIP-qPCR confirmed the differential allelic binding of IKZF3, CHD4, RBBP4, and IRF5. Silencing of IRF5 in CD8+ T cells increased the levels of IFNγ mRNA as measured by RT-qPCR (P = 0.03) and IFNγ protein as measured by ELISA (P = 0.02).ConclusionThese findings suggest that the association of rs4648889 with AS reflects allele-specific binding of this enhancer-like region to certain TFs, including IRF5, IKZF3, and members of the NuRD complex. IRF5 may have crucial influences on the functions of CD8+ lymphocytes, a finding that could reveal new therapeutic targets for the management of AS.

Dataset Information

The LMP2 CfoI polymorphism is associated with ankylosing spondylitis (AS) risk but not with acute anterior uveitis (AAU): A meta-analysis.

Publications

The LMP2 CfoI polymorphism is associated with ankylosing spondylitis (AS) risk but not with acute anterior uveitis (AAU): A meta-analysis.

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