ADIPOQ基因多态性与肝脏移植术后新发糖尿病的相关性分析

发布时间：2018-07-29 12:47

【摘要】：背景：肝脏移植经过50余年的发展,病人的预后得到了极大的改善。但是肝脏移植术后新发糖尿病的发病率一直居高不下,已经成为了影响患者远期生存率和生存质量的重要因素。研究发现糖尿病患者血浆中Adiponectin含量显著低于正常人群。本研究旨在通过基因遗传角度解释ADIPOQ单核苷酸位点突变可能参与了肝移植术后新发糖尿病的过程。方法：本研究包括了我中心256例2009年1月到2011年12月间接受肝脏移植的患者,并将其分为移植术后新发糖尿病组(New-onset Diabetes After Transplantation, NODAT)和移植术后非新发糖尿病组(Non-New-Onset Diabetes After Transplantation, Non-NODAT).通过单因素和多因素分析筛选出NODAT的危险因素。进一步地,根据多因素分析的结果建立NODAT的风险评估模型,并通过AUROC曲线得到优化的NODAT预测模型。再者,本研究分析了代谢综合症与NODAT之间的相关性。最后,通过Kaplan-Meier法分析NODAT对于患者术后总体生存率和移植物存活率的影响。结果：肝移植术后6月新发糖尿病的整体发病率为29%(75/181)。256例肝移植受体中,男性214名、女性42名,平均年龄为48.0±9.9岁。单因素分析得出年龄(54.0±4.1 vs 45.4±6.9, P0.001)、BMI (23.1±3.0 vs 22.3±3.0, P0.014)、移植术后1月他克莫司浓度(10.23±3.30 vs 8.76±1.74,P0.001)以及ADIPOQ rs1501299 (P0.007)和rs822396(P0.013)单核苷酸位点基因多态性为NODAT的危险因素。Dominant和Recessive模型多因素分析均证实并进一步筛选出这些危险因子。通过将上述危险因素进行分层建立NODAT风险评估模型,得到了包含有年龄、BMI、移植术后1月他克莫司浓度和rs1501299在内的优化预测模型(AUROC=0.743).代谢综合症与NODAT之间亦存在着显著相关性(21% vs 8%, P0.003)。 Kaplan-Meier法分析得到NODAT的总体生存率(P0.015)和移植物存活率(P0.011)均低于Non-NODAT组。结论：受体ADIPOQ rs1501299基因多态性与NODAT显著相关,可用于进行肝移植术后NODAT的发病风险评估预测。年龄、BMI指数和移植术后1月他克莫司水平为NODAT的危险因素,移植术后新发糖尿病患者在长期生存率和移植物存活率方面预后更差。
[Abstract]:Background: after more than 50 years of development, the prognosis of liver transplantation patients has been greatly improved. However, the incidence of new diabetes has been high after liver transplantation, which has become an important factor affecting the long-term survival rate and quality of life. The study found that plasma Adiponectin levels in diabetic patients were significantly lower than those in normal controls. The aim of this study was to explain the possible role of ADIPOQ single nucleotide mutation in the process of emerging diabetes mellitus after liver transplantation. Methods: this study included 256 patients with indirect liver transplantation from January 2009 to December 2011 in our center and were divided into new diabetic group (New-onset Diabetes After Transplantation, NODAT) and non-new diabetic group (Non-New-Onset Diabetes After Transplantation, Non-NODAT) after transplantation. The risk factors of NODAT were screened by single factor and multivariate analysis. Furthermore, according to the results of multi-factor analysis, the risk assessment model of NODAT is established, and the optimized NODAT prediction model is obtained by AUROC curve. Furthermore, this study analyzed the association between metabolic syndrome and NODAT. Finally, Kaplan-Meier method was used to analyze the effect of NODAT on the overall survival rate and graft survival rate. Results: the overall incidence of new diabetes mellitus in 6 months after liver transplantation was 29% (75 / 181). Among 256 recipients, 214 were males and 42 were females, with an average age of 48.0 卤9.9 years. Univariate analysis showed that age (54.0 卤4.1 vs 45.4 卤6.9, P0.001) BMI (23.1 卤3.0 vs 22.3 卤3.0, P0.014), tacrolimus concentration (10.23 卤3.30 vs 8.76 卤1.74 P0.001) and single nucleotide locus polymorphism of ADIPOQ rs1501299 (P0.007) and rs822396 (P0.013) were the risk factors of NODAT. These risk factors were further screened out. The risk assessment model of NODAT was established by stratification of the above risk factors, and an optimized predictive model (AUROC=0.743) was obtained, including the concentration of tacrolimus and rs1501299 in 1 month after transplantation. There was also a significant correlation between metabolic syndrome and NODAT (21% vs 8, P0.003). The overall survival rate (P0.015) and graft survival rate (P0.011) of NODAT were lower than those of Non-NODAT group. Conclusion: the polymorphism of receptor ADIPOQ rs1501299 gene is significantly associated with NODAT and can be used to predict the risk of NODAT after liver transplantation. Age index and tacrolimus level in 1 month after transplantation were risk factors of NODAT, and the prognosis of patients with new diabetes mellitus after transplantation was worse in terms of long-term survival rate and graft survival rate.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R657.3;R587.1

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