Prognostic Analysis And Genetic Research In Patients With Keshan Disease

Part ? The endemic status of Keshan disease in China and severe epidemic provinces.Objective: The purpose of our study was to describe the endemic status of KD in China and seven historically severe epidemic provinces.Methods: The data were collected by the national KD surveillance in 1990-2009 and the focal monitoring area survey after 2009,the moving average method and ARIMA model were used to predict data to fill the blank records.t test was used to analyze the each 5-year interval.Results: The KD detection and incidence rates were remained at low level,the detection rates of KD,latent KD,and chronic KD decreased significantly between 1995-2009 and 2000-2004(P<0.05),only those of chronic KD showed a significant increase between 1995-1999 and 2000-2004.Meanwhile,in terms of the incidence rates,there were no statistically significant differences(P>0.05)among each five-year period.All of the average chronic detection rates in seven historical severe epidemic provinces were lower than 0.1%.Conclusion: The detection and incidence rates of KD in the China and seven historical severe epidemic provinces had remained a low level.Part ? Clinical characteristics and prognosis of patients with Keshan diseaseObjective: The purpose of our study was to describe the clinical characteristics and prognosis of KD patients and to determine its independent risk factors.Methods: 92 patients with Keshan disease admitted to the local Disease Prevention and Control Center were retrospectively analyzed.Cox regression models and Kaplan-Meier survival curves were used to investigate risk factors of the all-cause mortality in KD patients.SPSS 21.0 software was used for statistical analysis.Results: In this study,the mean follow-up period of the 92 patients were 58.9 ± 23.0 months.The Cox univariate analysis showed that NYHA functional class,atrial fibrillation(AF),left ventricle(LV)and left atrium(LA)diameter at diagnosis contributed to increased risk of all-cause death.Cox multivariate analysis showed that LA diameter(HR=1.090,95%CI,1.032-1.151,P=0.002)were independent predictors of all-cause mortality in patients with KD.Conclusion: The prognosis of patients with Keshan disease was poor and patients with LA >37mm have a negative prognosis.Part ? Screen of Candidate Gene Mutations in patients with Keshan diseaseObjective: To screen the candidate gene mutations by using the whole exome sequencings in qualified DNA samples of patients with KD,which expected to find the new pathogenic or locus of KD.Methods: The clinical data of patients with Keshan disease were recorded and the samples of whole-blood were collected.Then,extracted DNA from the whole-blood samples in KD patients and the qualified DNA samples were collected.Gene mutation was examined by the whole-exome sequencing to detect the candidate pathogenic gene of KD.Results: In this study,we found a likely pathogenic frameshift variant on SEPHS2 gene,missense mutation on HELA gene in 8 KD patients with 3 nucleotide mutations appeared,missense mutation on PCDHA10 gene in 4 KD patients with 4 nucleotide mutations appeared,and missense mutation on PIEZO1 gene in 21 patients with 17 nucleotide mutations appeared,and in 25 patients with 10 Selenium-associated protein gene mutations.Conclusion: The genetic might be potential etiology of KD.