Study On 3'UTR Length Polymorphism Of Uremia Patients

Uremia was a kind of disease with high morbidity and high mortality,whose pathogenesis was complex.Symptoms of uremia could be long hidden,and the symptoms in different patients varied,and damages in different organs or tissues of different people were not the same.The diagnosis of uremia was not just based on serum creatinine levels,but also a variety of symptoms and supplementary detections.Early management,diagnosis and treatment of uremia were already public health problem with global concern.At present,there was still a great potential for further study on prediction,diagnosis and treatment of uremiaObject:Explore the pathogenesis of uremia by sequencing technology of alternative polyadenylation sites(SAPAS).Method:Select 10 uremia patients and 10 healthy human,take their peripheral blood mononuclear cells(PBMCs)as experimental samples.Length polymorphismin of 3' untranslated region of mRNA(3'UTR)in uremic sample was studied,and the different levels of gene expression between uremic group and the healthy control were analysed as well.By quantitative reverse transcription polymerase chain reaction(QRT-PCR),the results were validated.Result:Compared with the healthy control,691 genes in uremic group used significantly different 3'UTR length,in which 475 genes used shortened 3'UTR,and 216 genes used lengthened 3'UTR.Some 3'UTR lengthened genes and some 3'UTR shortened genes involved in the same GO terms.Different 3'UTR genes might enriched in the same GO terms,and number of such genes were different.792 genes were upregulated and 252 genes were downregulated.We did not observe a significant relationships between 3'UTR length and the expression level of the same genes.Combined with bioinformatics functional analysis,the paper explore the connection between 3'UTR length polymorphism,different gene expression levels and the clinical symptoms of Uremia.These genes involved in functions such as proteolytic ubiquitin mediated pathogenesis,insulin signaling pathway,B cell receptor signaling pathway,Notch signaling pathway,apoptosis,actin cytoskeleton regulation,vascular smooth muscle contraction,thrombomodulin and so on.These enriched genes not only affected renal function of the patients,but also involved in other complications and organ damage caused by disease.Conclusion:There was a complicated relationship between the 3'UTR length polymorphism and gene function.3'UTR involved in the regulation of gene expression mediated by miRNA,RNA binding proteins or other substances.This study was a new perspective to the pathogenesis of uremia.In this experiment,we achieved a genome-wide study of 3'UTR length polymorphism and identified hundreds of differentially expressed genes,which was helpful to find potential biomarkers for the early diagnosis,prognosis,targeted therapy of uremia,and to provide basic research for symptomatic treatment.