RESUMO
BACKGROUND: 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. AIM: 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. METHODS: The group studied consisted of 214 chronic HD patients prospectively followed up for 43 months. 100 patients died, 48 due to cardiovascular causes. RESULTS: 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). CONCLUSION: In summary, our study shows for the first time a link between RAGE and GLO polymorphisms in the prognosis of HD patients.
Assuntos
Produtos Finais de Glicação Avançada/genética , Falência Renal Crônica/genética , Falência Renal Crônica/mortalidade , Lactoilglutationa Liase/genética , Receptores Imunológicos/genética , Diálise Renal , Idoso , Feminino , Seguimentos , Predisposição Genética para Doença/epidemiologia , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/terapia , Lactoilglutationa Liase/metabolismo , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Prognóstico , Estudos Prospectivos , Receptor para Produtos Finais de Glicação Avançada , Receptores Imunológicos/metabolismo , Uremia/genética , Uremia/metabolismo , Uremia/terapiaRESUMO
Effect of advanced glycation end products (AGEs) in the pathogenesis of cancer could be diminished by interaction with soluble RAGE or by reducing AGE-precursors via glyoxalase I. Glu111Ala polymorphism of glyoxalase I gene, AGEs, and sRAGE serum levels were studied in 113 breast cancer patients and in 58 controls. Higher frequency of the mutated C allele was found in patients with negative estrogen receptors and in patients in clinical stage III compared to controls (P< 0.05). The presence of the C allele could represent a negative prognostic factor; however, further studies are needed to confirm this hypothesis.
Assuntos
Neoplasias da Mama/genética , Regulação Enzimológica da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Lactoilglutationa Liase/genética , Polimorfismo de Nucleotídeo Único , Idoso , Neoplasias da Mama/enzimologia , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Produtos Finais de Glicação Avançada/sangue , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Receptor para Produtos Finais de Glicação Avançada , Receptores de Estrogênio/análise , Receptores Imunológicos/sangueRESUMO
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.