PAI-1基因多态性与糖尿病肾病患者并发脑梗死的关系研究

Association between PAI-1 gene polymorphisms and cerebral infarction in patients with diabetic nephropathy

摘要:

目的 探讨纤溶酶原激活剂抑制物-1（PAI-1）基因多态性与糖尿病肾病（DN）患者并发脑梗死的关系。方法 回顾性2020年1月—2023年12月大庆龙南医院收治的149例DN患者的资料，其中DN并发脑梗死患者68例（DN并发脑梗死组）、单纯DN患者81例（DN未并发脑梗死组）。比较两组患者PAI-1基因多态性；采用多因素一般Logistic回归分析DN患者并发脑梗死的影响因素；采用受试者工作特征（ROC）曲线分析PAI-1基因多态性预测DN患者并发脑梗死的价值。结果 两组患者PAI-1基因的4G/4G、4G/5G和5G/5G基因频率比较，差异有统计学意义（P < 0.05）；DN并发脑梗死组PAI-1基因的4G/4G基因频率高于DN未并发脑梗死组。两组患者PAI-1基因的4G等位基因和5G等位基因构成比较，差异有统计学意义（P < 0.05）；DN并发脑梗死组的4G等位基因构成高于DN未并发脑梗死组（P < 0.05）。两组的性别构成、年龄、体质量指数、吸烟率、饮酒率、高血压患病率、高脂血症患病率、冠心病患病率、收缩压、舒张压、既往用药史构成、T2DM病程、糖化血红蛋白水平、心脑血管事件发生率、UAER水平、残余肾功能水平、24 h尿量、残余肾小球滤过率、CysC水平、血红蛋白水平、血清白蛋白水平、血肌酐水平、血尿酸水平、血尿素氮水平、血钙水平、血磷水平、空腹血糖水平、TG水平和HDL-C水平的比较，差异均无统计学意义（P > 0.05）。DN并发脑梗死组的透析龄、TC水平、LDL-C水平、纤维蛋白原水平、同型半胱氨酸水平均高于DN未并发脑梗死组（P < 0.05），DN并发脑梗死组的尿素清除指数低于DN未并发脑梗死组（P <0.05）。多因素一般Logistic回归分析显示，PAI-1基因4G/4G基因型［O^R=5.859（95% CI：2.003，17.142）］、透析龄大［O^R=4.545（95% CI：1.870，11.046）］、LDL-C水平高［O^R=3.951（95% CI：1.626，9.603）］均为DN患者并发脑梗死的危险因素（P <0.05）。ROC曲线结果显示，透析龄、LDL-C、PAI-1基因多态性单一及联合预测DN患者并发脑梗死的敏感性分别为77.78%（95% CI：0.676，0.853）、87.65%（95% CI：0.782，0.921）、85.19%（95% CI：0.750，0.921）、92.59%（95% CI：0.853，0.964），特异性分别为75.00%（95% CI：0.647，0.833）、70.59%（95% CI：0.600，0.800）、67.65%（95% CI：0.562，0.781）、85.29%（95% CI：0.765，0.914），曲线下面积分别为0.810（95% CI：0.740，0.880）、0.853（95% CI：0.790，0.916）、0.764（95% CI：0.684，0.844）、0.939（95% CI：0.900，0.978）。结论 PAI-1基因4G/4G基因型、透析龄、LDL-C与DN患者并发脑梗死有关，三者联合预测DN患者并发脑梗死的效能良好。

Abstract:

Objective To investigate the relationship between plasminogen activator inhibitor-1 (PAI-1) gene polymorphisms (4G/5G) and cerebral infarction (CI) in patients with diabetic nephropathy (DN).Methods Data from 149 DN patients admitted between January 2020 and December 2023 were reviewed: 68 with CI (CI group) and 81 without CI (non-CI group). PAI-1 4G/5G genotype and allele frequencies were determined. Clinical and laboratory data were compared. Multivariate logistic regression identified CI risk factors. ROC analysis evaluated the predictive value of PAI-1 polymorphisms alone and combined with other factors.Results Genotype (4G/4G, 4G/5G, 5G/5G) and allele (4G, 5G) distributions differed significantly between groups (P < 0.05). The CI group had a higher frequency of the 4G/4G genotype and 4G allele (P < 0.05). The CI group had longer dialysis vintage, higher TC, LDL-C, fibrinogen, homocysteine levels, and lower urea clearance index (Kt/V) (P < 0.05). Multivariate analysis identified 4G/4G genotype [O^R = 5.859 (95% CI: 2.003, 17.142) ], longer dialysis vintage [O^R = 4.545 (95% CI: 1.870, 11.046) ], and high LDL-C [O^R = 3.951 (95% CI: 1.626, 9.603) ] as independent risk factors for CI. ROC analysis showed sensitivities for dialysis vintage, LDL-C, PAI-1 polymorphism, and their combination predicting CI were 77.78% (95% CI: 0.676, 0.853), 87.65% (95% CI: 0.782, 0.921), 85.19% (95% CI: 0.750, 0.921), and 92.59% (95% CI: 0.853, 0.964), respectively. Specificities were 75.00% (95% CI: 0.647, 0.833), 70.59% (95% CI: 0.600, 0.800), 67.65% (95% CI: 0.562, 0.781), and 85.29% (95% CI: 0.765, 0.914), respectively. AUCs were 0.810 (95% CI: 0.740, 0.880), 0.853 (95% CI: 0.790, 0.916), 0.764 (95% CI: 0.684, 0.844), and 0.939 (95% CI: 0.900, 0.978), respectively.Conclusion The PAI-1 4G/4G genotype, dialysis vintage, and LDL-C are associated with CI in DN patients. Their combination demonstrates excellent predictive performance.