湘赣地区汉族人群人类白细胞抗原与肾移植后糖尿病的相关性

Correlation between human leukocyte antigen and post-transplantation diabetes mellitus in Han population from Hunan and Jiangxi provinces

背景:移植后糖尿病也具有2型糖尿病的高度遗传异质性的特点,湘赣地区汉族人群人类白细胞抗原(HLA)与移植后糖尿病相关性研究领域尚属空白。目的:分析湘赣地区肾移植患者HLA与移植后糖尿病的相关性,确定该地区人群移植后糖尿病的易感基因和保护基因,并为肾移植后个体化用药提供参考数据。设计、时间及地点:调查分析,于2007-05/2008-07在中南大学湘雅二医院泌外器官移植科完成。对象:收集中南大学湘雅二医院泌外器官移植科2003/2008接受肾移植患者的个人信息资料、移植前后各项检查结果、配型资料等,并进行随访登记。共收集得符合条件的患者共195例,其中移植后糖尿病患者22例,非移植后糖尿病移植受者173例。方法:使用χ2检验对移植后糖尿病组与非移植后糖尿病组患者各HLA抗原的出现频率进行比较分析;根据移植后使用的钙调神经蛋白抑制药物类药物不同将195例患者分成环孢素A组和他克莫司组,通过χ2检验对这两组患者移植后糖尿病的发生率进行比较;根据患者年龄,将其分为高龄组(≥40岁)和非高龄组(<40岁),通过χ2检验对这两组患者移植后糖尿病的发病率进行比较。主要观察指标:所有患者定期随访,随访项目为年龄、血压、尿量、血尿常规、肝肾功能、血糖及血药浓度。结果:HLA-A30和HLA-DR7可能是湘赣地区汉族人群移植后糖尿病的易感基因,未发现对移植后糖尿病具有明显保护作用的基因。在使用小剂量、低血药浓度钙调神经蛋白抑制药物类药物预防排斥反应情况下,环孢素A组患者和他克莫司组患者移植后糖尿病的发病率差异无显著性意义(P>0.05);高龄移植受者移植后糖尿病的发生率显著高于低龄移植受者(P<0.05)。结论:HLA-A30和HLA-DR7可能是湖南和江西部分地区汉族人群移植后糖尿病的易感基因,对于携带这两种基因的移植受者,有必要在移植后密切监测血糖、尿糖,适时调整免疫抑制药物的种类和用量;在小剂量低浓度的使用原则下,他克莫司并不明显增加移植后糖尿病的发生率;高龄患者移植后糖尿病发生率显著增加,加之高龄患者本身已有的基础性心脑血管疾病的发病率升高,罹患移植后糖尿病更易导致心脑血管事件的发生,因此,对高龄移植受者进行常规的血糖和尿糖的监测和控制,并建立个体化的免疫抑制方案就显得更为重要。

BACKGROUND：Post-transplantation diabetes mellitus has the same characteristics as type II diabetes mellitus;however,correlation between human leucocyte antigen （HLA） and post-transplantation diabetes mellitus remains unclear among Han population in Hunan and Jiangxi provinces.OBJECTIVE：To analyze the correlation between HLA and post-transplantation diabetes mellitus,to determine predisposing genes and protecting genes of post-transplantation diabetes mellitus,and to provide reference data for personalized medicine of post-transplantation diabetes mellitus.DESIGN,TIME AND SETTING：A survey analysis was performed at Department of Urological Organ Transplantation,the Second Xiangya Hospital of Central South University from May 2007 to July 2008.PARTICIPANTS：Patients with kidney transplantation selected from Department of Urological Organ Transplantation,the Second Xiangya Hospital of Central South University between 2003 and 2008 were followed-up on individual information,testing results before and after transplantation,and zygosity.Among 195 included cases,there were 22 patients with post-transplantation diabetes mellitus and 173 with non-post-transplantation diabetes mellitus.Methods：METHODS：χ^2 was used to compare frequency of HLA antigen between post-transplantation diabetes mellitus and non-post-transplantation diabetes mellitus groups.The 195 patients were divided into ciclosporin A group and tacrolimus group according to immunosuppressive regimen,and the incidence of post-transplantation diabetes mellitus were compared usingχ2 test.All the patients were then divided into elderly group （age ≥ 40） and low-age group （age〈40）,and the incidences of post-transplantation diabetes mellitus were calculated and compared using χ^2 test.MAIN OUTCOME MEASURES：Following-up was performed including age,blood pressure,urine volume,blood and urine routine test,liver and kidney function,blood glucose,and blood drug level.RESULTS：HLA-A30 and HLA-DR7 might be the predisposing genes of post-transplantation diabetes mellitus in south China;however,protecting genes were not found.Low dosage and low blood drug level of calcineurin inhibitors were applied in this study,and there was no significant difference in the incidence of post-transplantation diabetes mellitus between ciclosporin A and tacrolimus groups （P 〉0.05）.The incidence of post-transplantation diabetes mellitus in elderly group was significantly higher than that in low-age group （P〈 0.05）.CONCLUSION：HLA-A30 and HLA-DR7 might be the predisposing genes of post-transplantation diabetes mellitus in south China;therefore,they should be paid much attention on levels of blood glucose and urine glucose after transplantation so as to adjust the types and dosages of immunosuppressive drug in time.Low-dosage and low-concentration tacrolimus was not increased incidence of post-transplantation diabetes mellitus remarkably.However,the incidence of post-transplantation diabetes mellitus in the elderly patients was high;moreover,the incidence of cardio-cerebrovascular disease was also high.Therefore,post-transplantation diabetes mellitus might easily cause the onset of cardio-cerebrovascular disease.It was important for elderly patients to monitor blood glucose and urine glucose levels and set up an individual immunosuppression program following transplantation.