BackgroundAgeing brings about the gradual deterioration of the immune system, also known as immunosenescence. The role of non-coding circular RNA in immunosenescence is under studied. Using circular RNA microarray data, we assembled Comparison groups (C1, C2, C3 and C4) that allowed us to compare the circular RNA expression profiles between CD28(+)CD8(+) T cells and CD28(-)CD8(+) T cells isolated from healthy elderly or adult control subjects. Using a step-wise biomathematical strategy, the differentially-expressed circRNAs were identified in C1 (CD28(+)CD8(+) vs CD28(-)CD8(+)T cells in the elderly) and C4 (CD28(-)CD8(+)T cells in the elderly vs in the adult), and the commonly-expressed circRNA species from these profiles were optimized as immunosenescence biomarkers.ResultsFour overlapping upregulated circular RNAs (100550, 100783, 101328 and 102592) expressed in cross-comparison between C1 and C4 were validated using quantitative polymerase chain reaction. Of these, only circular RNA100783 exhibited significant validation. None of the down-regulated circular RNAs were expressed in the C1 and the C4 cross-comparisons. Therefore, we further predicted circular RNA100783-targeted miRNA-gene interactions using online DAVID annotation. The analysis revealed that a circular RNA100783-targeted miRNA-mRNA network may be involved in alternative splicing, the production of splice variants, and in the regulation of phosphoprotein expression. Considering the hypothesis of splicing-related biogenesis of circRNAs, we propose that circular RNA100783 may play a role in phosphoprotein-associated functions duringCD28-related CD8(+) T cell ageing.ConclusionsThis study is the first to employ circular RNA profiling to investigate circular RNA-micro RNA interactions in ageing human CD8(+)T cell populations and the accompanying loss of CD28 expression. The overlapping expression of circular RNA100783 may represent a novel biomarker for the longitudinal tracking ofCD28-related CD8(+) T cell ageing and global immunosenescence.Electronic supplementary materialThe online version of this article (doi:10.1186/s12979-015-0042-z) contains supplementary material, which is available to authorized users.
A genome-wide association study (GWAS) suggested that variants on chromosome 17q21 were associated with childhood-onset asthma in white populations. Two replication studies had been conducted in southern Han Chinese population in 2009 and 2012. However, these two Chinese replication results were inconsistent. To further confirm the role of 17q21 common variants, an association study of 17q21 single nucleotide polymorphisms (SNPs) with the risk of childhood-onset asthma was performed in a Han population from northeastern China. In this study, rs3894194, rs12603332 and rs11650680 were genotyped in 435 asthmatic children and 601 healthy controls by using a SNaPshot method. Our data showed that the allelic frequency of rs12603332 and rs11650680 showed significant differences between asthmatic cases and healthy controls, with an odds ratio (OR) of 1.36 [95% confidence interval (CI) 1.12-1.65, P=0.002] and an OR of 1.36 (95% CI 1.07-1.74, P=0.01). Genotype distribution analysis also showed the significant associations of the above two loci with childhood asthma under dominant, recessive and additive model (dominant OR=1.57, 95% CI 1.04-2.36, P=0.032; recessive OR=1.41, 95% CI 1.09-1.83, P=0.009; additive OR=1.97, 95% CI 1.24-3.14, P=0.004; recessive OR=1.50, 95% CI 1.13-1.98, P=0.005). Besides, linear regression analysis showed that rs3894194 and rs12603332 were also significantly associated with asthma phenotypes such as log10 -transformed immunoglobulin E (IgE) level (IU/ml) and log10 -transformed eosinophil percentage (dominant, P=0.04; additive, P=0.01; recessive, P=0.04; recessive, P=0.03; additive, P=0.02). Collectively, our findings suggest that orosomucoid 1-like 3 (ORMDL3) locus on chromosome 17q21 is a risk factor for childhood-onset asthma in northeastern Han Chinese population. Further studies will be needed to elucidate the pathogenesis that ORMDL3 locus predisposes to childhood-onset asthma.
Objective
To systematically review the relationship between genotypes and clinical phenotypes of Familial exudative vitreoretinopathy (FEVR) to support risk estimation and therapeutic decisions.
Design
Systematic review with meta-analysis.
Data sources
The data of our study were collected from PubMed, Embase, Web of Science, Cochrane, CBM, China National Knowledge Infrastructure (CNKI), WAN FANG and VIP databases since inception to August 2021.
Results
A total of 3257 patients from 32 studies were included according to the inclusion and exclusion criteria. Among all the cases, the mutation frequencies of LRP5, FZD4, NDP, TSPAN12, ZNF408 and KIF11 were 13.6%, 11.5%, 4.6%, 6.7%, 1.6%, and 5.7%, respectively. We found that the patients with NDP and FZD4 suffer more severe symptoms, among which 86.4% patients of NDP and 78.6% patients of FZD4 were in the advanced stage of FEVR. Retinal detachment is the most frequent symptom with patients of LRP5 and NDP mutations, accounting for 51.9% and 64.5%, respectively. For the patients with the mutation of TSPAN12, retinal fold is the most common clinical manifestation, and suffer the mildest clinical phenotypes compared with the other three genes.
Conclusion
The results of the meta-analysis indicate that different types of genetic mutations occur at different frequencies. In addition, the clinical manifestations of FEVR are related to the type of gene mutation. Therefore, targeted treatment strategies and follow-up recommendations should be adopted for different pathogenic genes of FEVR.
The asymmetric Michael addition of phosphorus nucleophiles to electron-deficient alkenes is one of the most direct and atom-economical methods to provide chiral organophosphorus compounds with high efficiency in recent years....
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