Correlation between metabolic markers and blood lipid levels in kidney transplant recipients
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摘要:
目的 分析肾移植受者血脂代谢、高脂血症、他克莫司药物代谢中共表达的基因及其与血脂水平的相关性。 方法 从比较毒理基因组学数据库（CTD）中筛选出共表达的基因。收集25例肾移植受者的一般资料，检测ATP结合盒亚家族A成员1（ABCA1）、过氧化物酶体增殖物激活受体γ（PPAR-γ）、糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白1（GPIHBP1）的表达情况。对肾移植受者进行跟踪随访，收集术后1、3、6、12个月空腹血糖、糖化血红蛋白、甘油三酯、总蛋白、白蛋白、球蛋白、胆固醇、高密度脂蛋白、低密度脂蛋白、他克莫司血药浓度，并分析受者高脂血症的发生情况。分析ABCA1、GPIHBP1、PPAR-γ与临床指标的相关性，及其与相关指标对肾移植术后高脂血症的诊断效能。 结果 共筛选出3个共表基因ABCA1、PPAR-γ、GPIHBP1。ABCA1与术后6个月胆固醇、术后3个月他克莫司血药浓度成正相关，与术后3个月空腹血糖呈负相关（均为P<0.05）；GPIHBP1与术前胆固醇、术前甘油三酯呈负相关，与术后3个月他克莫司血药浓度呈正相关（均为P<0.05）。PPAR-γ与术前球蛋白、术前低密度脂蛋白呈负相关（均为P<0.05）。ABCA1、GPIHBP1、PPAR-γ联合术前球蛋白及术后1、6个月血糖水平诊断肾移植术后高甘油三酯血症的效果较好（AUC=0.900）。ABCA1、GPIHBP1、PPAR-γ联合术后1、6个月他克莫司血药浓度及术后6个月血糖水平诊断肾移植术后高胆固醇血症的效果较好（AUC=0.931）。 结论 ABCA1、GPIHBP1、PPAR-γ与肾移植术后血脂、他克莫司血药浓度等指标存在不同程度的相关关系，但用于预测肾移植术后高脂血症尚无确切依据。提升机体免疫力、规范的血糖管理可能是控制高脂血症的有益因素。 -
关键词:
- 肾移植 /
- 高脂血症 /
- 胆固醇 /
- 甘油三酯 /
- 他克莫司 /
- ATP结合盒亚家族A成员1（ABCA1） /
- 过氧化物酶体增殖物激活受体γ（PPAR-γ） /
- 糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白1（GPIHBP1）
Abstract:Objective To analyze the co-expressed genes in blood lipid metabolism, hyperlipidemia and tacrolimus metabolism and their correlation with blood lipid levels in kidney transplant recipients. Methods Co-expressed genes were screened from Comparative Toxicogenomic Database (CTD). Baseline data of 25 kidney transplant recipients were collected. The expression levels of ATP binding cassette subfamily A member 1(ABCA1), peroxisome proliferator activated receptor γ (PPAR-γ) and glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1 (GPIHBP1) were measured. All recipients were followed up. The concentrations of fasting blood glucose, glycosylated hemoglobin, triglyceride, total protein, albumin, globulin, cholesterol, high-density lipoprotein, low-density lipoprotein and tacrolimus blood concentration were collected at postoperative 1, 3, 6 and 12 months, and the incidence of hyperlipidemia in the recipients was analyzed. The correlation between ABCA1, GPIHBP1, PPAR-γ and clinical indexes was assessed. The diagnostic efficiency of related indexes for hyperlipidemia after kidney transplantation was evaluated. Results Three co-expressed genes including ABCA1, PPAR-γ and GPIHBP1 were screened. ABCA1 was positively correlated with cholesterol level at postoperative 6 months and tacrolimus blood concentration at postoperative 3 months, whereas negatively correlated with fasting blood glucose level at postoperative 3 months (all P<0.05). GPIHBP1 was negatively correlated with preoperative cholesterol and triglyceride levels, whereas positively correlated with tacrolimus blood concentration at postoperative 3 months (all P<0.05). PPAR-γ was negatively correlated with preoperative globulin and low-density lipoprotein levels (both P<0.05). ABCA1, GPIHBP1 and PPAR-γ combined with preoperative globulin and blood glucose level at postoperative 1 and 6 months after operation yielded high diagnostic efficiency for hypertriglyceridemia after kidney transplantation (AUC=0.900). ABCA1, GPIHBP1 and PPAR-γ combined with tacrolimus blood concentrations at postoperative 1 and 6 months and blood glucose level at postoperative 6 months had high diagnostic efficiency for hypercholesterolemia after kidney transplantation (AUC=0.931). Conclusions ABCA1, GPIHBP1 and PPAR-γ are correlated with blood lipid level and tacrolimus blood concentration after kidney transplantation to different degrees. No definite evidence has been supported for predicting hyperlipidemia after kidney transplantation. Immunity improvement and rational blood glucose management may be beneficial factors for hyperlipidemia control. -
图 2 ABCA1与临床指标之间的相关性分析
注：A图为ABCA1与术后6个月胆固醇的相关性分析；B图为ABCA1与术后3个月他克莫司血药浓度的相关性分析；C图为ABCA1与术后3个月空腹血糖的相关性分析。
Figure 2. Correlation analysis between ABCA1 and clinical indexes
图 3 GPIHBP1与临床指标之间的相关性分析
注：A图为GPIHBP1与术前胆固醇的相关性分析；B图为GPIHBP1与术前甘油三酯的相关性分析；C图为GPIHBP1与术后3个月他克莫司血药浓度的相关性分析。
Figure 3. Correlation analysis between GPIHBP1 and clinical indexes
图 4 PPAR-γ与临床指标的相关性分析
注：A图为PPAR-γ与术前球蛋白的相关性分析；B图为PPAR-γ与术前低密度脂蛋白的相关性分析。
Figure 4. Correlation analysis between PPAR-γ and clinical indexes
图 5 各指标对肾移植术后高甘油三酯血症的诊断效能
注：A图为术前白蛋白、球蛋白、总蛋白、糖化血红蛋白诊断肾移植术后高甘油三酯血症的ROC曲线；B图为术前糖化血红蛋白、空腹血糖，术后1、3、6、12个月空腹血糖诊断肾移植术后高甘油三酯血症的ROC曲线；C图为术后首次，术后1、3、6、12个月他克莫司血药浓度诊断肾移植术后高甘油三酯血症的ROC曲线；D图为ABCA1、GPIHBP1、PPAR-γ诊断肾移植术后高甘油三酯血症的ROC曲线；E图为ABCA1、GPIHBP1、PPAR-γ联合诊断肾移植术后高甘油三酯血症的ROC曲线；F图为ABCA1、GPIHBP1、PPAR-γ联合术后1、6个月空腹血糖及术前球蛋白诊断肾移植术后高甘油三酯血症的ROC曲线。
Figure 5. Diagnostic efficacy of indicators for hypertriglyceridemia after kidney transplantation
图 6 各指标对肾移植术后高胆固醇血症的诊断效能
注：A图为术前白蛋白、球蛋白、总蛋白、糖化血红蛋白诊断肾移植术后高胆固醇血症的ROC曲线；B图为术前糖化血红蛋白、空腹血糖，术后1、3、6、12个月空腹血糖诊断肾移植术后高胆固醇血症的ROC曲线；C图为术后首次，术后1、3、6、12个月他克莫司血药浓度诊断肾移植术后高胆固醇血症的ROC曲线；D图为ABCA1、GPIHBP1、PPAR-γ诊断肾移植术后高胆固醇血症的ROC曲线；E图为ABCA1、GPIHBP1、PPAR-γ联合诊断肾移植术后高胆固醇血症的ROC曲线；F图为ABCA1、GPIHBP1、PPAR-γ联合术后1、6个月他克莫司血药浓度及术后6个月空腹血糖水平诊断肾移植术后高胆固醇血症的ROC曲线。
Figure 6. Diagnostic efficacy of indicators for hypercholesterolemia after kidney transplantation
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