Institute of Clinical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Prague, Czech Republic.
Kidney Blood Press Res. 2010;33(1):30-6. doi: 10.1159/000285845. Epub 2010 Feb 23.
Advanced glycation end products (AGEs) belong to uremic toxins and some pathological effects of AGEs are linked to RAGE (receptor for AGEs). Their precursors are detoxified by the glyoxalase (GLO) system. The A419C (E111A) polymorphism of the GLO I gene is associated with vascular disease in hemodialysis (HD) patients and some RAGE gene polymorphisms are implicated in various pathological states.
To study the relationship of A419C GLO I and four RAGE polymorphisms (-429T/C, -374T/A, 2184A/G and Gly82Ser) in the prognosis of HD patients.
The group studied consisted of 214 chronic HD patients prospectively followed up for 43 months. 100 patients died, 48 due to cardiovascular causes.
The Kaplan-Meier analysis showed a higher mortality rate in patient-mutated homozygotes for RAGE -429CC, RAGE 2184GG and GLO I 419CC. A higher hazard risk was confirmed by the Cox proportional hazards model when wild-type homozygotes were taken as reference: RAGE -429CC 2.28 (95% CI 1.04-4.99), RAGE 2184GG 3.16 (95% CI 1.44-6.93), and GLO I 419CC 1.75 (95% CI 1.08-2.86). Both RAGE polymorphisms were also associated with cardiovascular mortality: RAGE -429CC 3.54 (95% CI 1.37-9.14) and RAGE 2184GG 5.04 (95% CI 1.93-13.11).
In summary, our study shows for the first time a link between RAGE and GLO polymorphisms in the prognosis of HD patients.
晚期糖基化终产物（AGEs）属于尿毒症毒素，AGEs 的一些病理作用与 RAGE（AGEs 受体）有关。其前体通过糖氧还蛋白（GLO）系统解毒。GLO I 基因的 A419C（E111A）多态性与血液透析（HD）患者的血管疾病有关，而一些 RAGE 基因多态性与各种病理状态有关。
研究 GLO I 基因的 A419C 和 RAGE 基因的四个多态性（-429T/C、-374T/A、2184A/G 和 Gly82Ser）与 HD 患者预后的关系。
本研究纳入 214 例前瞻性随访 43 个月的慢性 HD 患者。100 例患者死亡，其中 48 例死于心血管原因。
Kaplan-Meier 分析显示，RAGE-429CC、RAGE-2184GG 和 GLO I-419CC 患者的突变纯合子死亡率较高。Cox 比例风险模型证实，当以野生型纯合子为参考时，风险比更高：RAGE-429CC 2.28（95%CI 1.04-4.99）、RAGE-2184GG 3.16（95%CI 1.44-6.93）和 GLO I-419CC 1.75（95%CI 1.08-2.86）。两种 RAGE 多态性也与心血管死亡率相关：RAGE-429CC 3.54（95%CI 1.37-9.14）和 RAGE-2184GG 5.04（95%CI 1.93-13.11）。
总之，我们的研究首次表明，在 HD 患者的预后中，RAGE 和 GLO 多态性之间存在关联。
