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首页> 外文期刊>Nephrology, dialysis, transplantation: official publication of the European Dialysis and Transplant Association - European Renal Association >Predictive role of multilocus genetic polymorphisms in cardiovascular disease and inflammation-related genes on chronic kidney disease in Type 2 diabetes-an 8-year prospective cohort analysis of 1163 patients
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Predictive role of multilocus genetic polymorphisms in cardiovascular disease and inflammation-related genes on chronic kidney disease in Type 2 diabetes-an 8-year prospective cohort analysis of 1163 patients

机译：多位点基因多态性在2型糖尿病慢性肾脏病中的心血管疾病和炎症相关基因在慢性肾脏疾病中的预测作用-对1163名患者的8年前瞻性队列分析

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Background.Chinese diabetic patients are at greater risk of developing chronic kidney disease (CKD) than Caucasian counterparts. In this hypothesis-generating study, we examined the independent and joint effects of multiple genetic variants on CKD in a prospective Chinese cohort of Type 2 diabetic patients. Methods.Seventy-seven single-nucleotide polymorphisms (SNPs) of 54 candidate genes for cardiorenal diseases and inflammation were genotyped in 1163 patients with no past history of CKD at baseline. CKD was defined as the first estimated glomerular filtration rate 60mL/min/1.73m 2 or the first hospitalization with a diagnosis of renal disease. Results.In Cox-regression analysis, 15 SNPs of 13 genes were associated with incident CKD. After correction for multiple comparisons, 6 SNPs including PON1 55Met, PON2 311Cys CETP-629C, ITGA2 873A, LTA 26Asn and LTA 252Gly remained independently associated with CKD, with respective hazard ratios (95% confidence interval):2.6 (1.4-4.8, P = 0.002), 1.5 (1.2-1.9, P = 0.003), 1.4 (1.1-1.7, P = 0.001), 2.2 (1.3-3.7, P = 0.002), 1.6 (1.1-2.2, P = 0.008) and 1.5 (1.1-2.1, P = 0.019). Analysis of joint effect of the six SNPs showed stepwise increase in risk of CKD with the accumulation of risk alleles and weighted genetic risk score (Ptrend = 8.9 × 10 -7 and 4.0 × 10 -5, respectively). Conclusions.In Type 2 diabetes, there are independent and joint effects of multiple genetic variants on risk of CKD. Risk associations with PON1, PON2, CETP, ITGA2 and LTA genetic polymorphisms underline the importance of lipid metabolism, haemostasis and inflammation in the development of CKD in patients with Type 2 diabetes.
机译：背景：中国糖尿病患者患慢性肾脏病（CKD）的风险比白种人高。在这项假设产生的研究中，我们研究了预期的中国2型糖尿病患者队列中多种遗传变异对CKD的独立和联合作用。方法：对1163例基线无CKD病史的患者进行了54种心血管疾病和炎症候选基因的77个单核苷酸多态性（SNP）的基因分型。 CKD定义为首次估计的肾小球滤过率<60mL / min / 1.73m 2或诊断为肾脏疾病的首次住院。结果：在Cox回归分析中，有13个基因的15个SNP与入射CKD相关。经过多次比较校正后，包括PON1 55Met，PON2 311Cys CETP-629C，ITGA2 873A，LTA 26Asn和LTA 252Gly在内的6个SNP仍与CKD独立相关，各自的危险比（95％置信区间）：2.6（1.4-4.8，P = 0.002），1.5（1.2-1.9，P = 0.003），1.4（1.1-1.7，P = 0.001），2.2（1.3-3.7，P = 0.002），1.6（1.1-2.2，P = 0.008）和1.5（ 1.1-2.1，P = 0.019）。六个SNP的联合作用分析显示，随着风险等位基因的积累和加权遗传风险评分的增加，CKD风险逐步增加（Ptrend分别为8.9×10 -7和4.0×10 -5）。结论：在2型糖尿病中，多种遗传变异对CKD风险具有独立和联合的影响。与PON1，PON2，CETP，ITGA2和LTA遗传多态性的风险相关性突出了2型糖尿病患者中脂质代谢，止血和炎症在CKD发生中的重要性。

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