Kalousová Marta, Germanová Alexandra, Jáchymová Marie, Mestek Oto, Tesar Vladimír, Zima Tomás
Institute of Clinical Chemistry and Laboratory Diagnostics, First Faculty of Medicine and General University Hospital, Charles University, Prague, Czech Republic.
Ann N Y Acad Sci. 2008 Apr;1126:268-71. doi: 10.1196/annals.1433.012. Epub 2007 Dec 13.
Advanced glycation end products (AGEs) take part in the pathogenesis of vascular, diabetic, and uremic complications. Their precursors are detoxified by the glyoxalase system. Our aim was to study A419C (E111A) single nucleotide polymorphism (SNP) of the glyoxalase I gene in hemodialysis (HD) patients. A419C SNP, several laboratory parameters including soluble receptor for AGEs (sRAGE), and clinical data were studied in 214 HD patients and 89 controls. Allelic and genotypic frequencies did not differ between HD patients and controls. A419C SNP was significantly linked with serum sRAGE, which sensitively reflects the AGE burden of the organism (3986 +/- 1638 pg/mL in the CC variant versus 3277 +/- 1398 pg/mL in the AC variant and 3297 +/- 1445 pg/mL in the AA variant, P < 0.01). In the CC variant, significantly higher prevalence of cardiovascular disease and peripheral vascular disease was found, while the prevalence of hypertension, diabetes mellitus, and dyslipidemia did not differ between genotypes. In summary, in this study we demonstrate for the first time the association of A419C polymorphism of the glyoxalase I gene with sRAGE levels and show the genetic predisposition to vascular complications in HD patients.
晚期糖基化终末产物（AGEs）参与血管、糖尿病和尿毒症并发症的发病机制。其前体可通过乙二醛酶系统解毒。我们的目的是研究血液透析（HD）患者乙二醛酶I基因的A419C（E111A）单核苷酸多态性（SNP）。对214例HD患者和89例对照者研究了A419C SNP、包括可溶性AGE受体（sRAGE）在内的多项实验室参数以及临床资料。HD患者与对照者之间的等位基因和基因型频率无差异。A419C SNP与血清sRAGE显著相关，sRAGE能敏感反映机体的AGE负荷（CC变异型为3986±1638 pg/mL，AC变异型为3277±1398 pg/mL，AA变异型为3297±1445 pg/mL，P<0.01）。在CC变异型中，心血管疾病和外周血管疾病的患病率显著更高，而不同基因型之间高血压、糖尿病和血脂异常的患病率无差异。总之，在本研究中我们首次证明乙二醛酶I基因的A419C多态性与sRAGE水平相关，并显示HD患者存在血管并发症的遗传易感性。
