A419C (E111A) Polymorphism of the Glyoxalase I Gene and Vascular Complications in Chronic Hemodialysis Patients

Abstract

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.

Genetic Predisposition to Advanced Glycation End Products Toxicity Is Related to Prognosis of Chronic Hemodialysis Patients

“…Genotype frequencies of both RAGE and GLO I gene polymorphisms have been described in our earlier publications [19,20] . For a better overview of further results, see table 2 .…”

“…All studied polymorphisms were assessed by PCR-RFLP (polymerase chain reaction-restriction fragment length polymorphism) and for selected samples confirmed by direct sequencing of the PCR product as described previously [19,20] . Genotype frequencies of both RAGE and GLO I gene polymorphisms have been described in our earlier publications [19,20] .…”

“…The borderline relationship to cardiovascular mortality (p = 0.084) might also be explained by the fact that judgement of the cause of death is very difficult, although two independent physicians were engaged. Another limitation is that genotype frequencies of GLO I polymorphism, unlike all RAGE polymorphisms studied [20] , were not in Hardy-Weinberg equilibrium [19] . However, this is in line with findings for other older and younger populations [30] , suggesting the existence of some selection forces.…”

“…amplification of the inflammatory response [14] , diabetic complications [15,16] , or coronary atherosclerosis [17,18] . Additionally, the A419C (E111A) polymorphisms of the GLO I gene were found to be associated with vascular disease in HD patients [19] .…”

“…Another study did not show any association of this SNP with the risk for Alzheimer's disease in the overall population [30] . Our previous study disclosed an association of this polymorphism with vascular disease in HD patients, either cardiovascular or peripheral vascular ones, and to sRAGE levels [19] . This GLO I polymorphism was also of significance in the prognosis of HD patients as shown in Cox regression and less clearly in Kaplan-Meier analysis (p = 0.055: borderline significance in log-rank test, however significant in Breslow test: p !…”