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1.
Clin Nephrol ; 74(5): 343-5, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20979941

RESUMO

BACKGROUND: pre-clinical studies showed that carnosine may have a beneficial cardiovascular effect. We studied the effect of tri-nucleotide repeat (CTGs) polymorphisms in exon 2 of the CNDP1 gene, which codes for carnosinase and is responsible for the degradation of carnosine, on the clinical outcome of Chinese peritoneal dialysis (PD) patients. METHODS: we studied 442 PD subjects. Genotyping was done by direct sequencing of genomic DNA. Patients were followed for 43.5 ± 16.2 months. RESULTS: the prevalence of 6-6, 5-6, 5-5 and 4-6 CTGs genotypes was 80.3%, 18.6%, 0.9% and 0.2%, respectively. A total of 270 patients (61.1%) developed the primary composite end point during follow-up. The 5-year event-free survival of the 6-6 CTGs and non 6-6 group was 37.1% and 21.3%, respectively (log rank test, p = 0.3). CONCLUSION: the CTGs polymorphism of the CNDP1 gene does not affect survival of Chinese PD subjects. The role of carnosine and CNDP1 gene polymorphism in the pathogenesis of cardiovascular disease requires further study.


Assuntos
Povo Asiático/genética , Dipeptidases/genética , Diálise Peritoneal , Polimorfismo Genético , Insuficiência Renal/terapia , Análise de Variância , Distribuição de Qui-Quadrado , China , Intervalo Livre de Doença , Éxons , Frequência do Gene , Genótipo , Humanos , Estimativa de Kaplan-Meier , Leucina , Diálise Peritoneal/efeitos adversos , Diálise Peritoneal/mortalidade , Fenótipo , Insuficiência Renal/enzimologia , Insuficiência Renal/etnologia , Insuficiência Renal/genética , Insuficiência Renal/mortalidade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Repetições de Trinucleotídeos
2.
Clin Nephrol ; 73(1): 44-50, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20040351

RESUMO

BACKGROUND: Interaction of receptor for advanced glycation end products (RAGE) with advanced glycation end products (AGEs) is an important pathogenic mechanism of diabetic complications. Three mutations in the promoter region of the RAGE gene (T-429C, T-374A and a 63 bp deletion spanning from -407 to -345 nucleotides) were known to have increased transcriptional activities. We investigated the relationship between these polymorphisms and the risk of cardiovascular diseases in Chinese subjects with overt diabetic nephropathy. METHODS: A total of 219 Type 2 diabetic subjects with nephropathy were recruited. Genotyping of the three polymorphisms in the genomic DNA was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Patients were followed for 8 years for the development of cardiovascular events and survival. RESULTS: The T-429 C and T-374 A polymorphism had no effect on the event-free survival of the subjects. For the 63 bp deletion polymorphism, the event-free survival was 37.0% and 63.2% at 96 months for del-/- and del-/+ genotypes, respectively (log-rank test, p = 0.034). After adjusting for confounders, the 63 bp deletion polymorphism had a marginal effect on event-free survival (adjusted hazard ratio: 3.517, 95% CI: 0.852 - 14.521, p = 0.082). Subjects without any mutation of the three polymorphisms have significantly higher risk of first ischemic heart disease than those with any of the three mutations (adjusted hazard ratio: 0.218, 95% CI: 0.062 - 0.764, p = 0.017). CONCLUSION: The 63 bp del-/+ genotype of the RAGE gene has a marginal benefit on the cardiovascular event-free survival in subjects with diabetic nephropathy. Subjects with any of the three mutations have a lower risk of ischemic heart disease. The role of RAGE in the pathogenesis of cardiovascular disease in diabetic patients requires further study.


Assuntos
Doenças Cardiovasculares/genética , Nefropatias Diabéticas/genética , Falência Renal Crônica/genética , Receptores Imunológicos/genética , Análise de Variância , Povo Asiático/genética , Doenças Cardiovasculares/etiologia , Distribuição de Qui-Quadrado , China , Nefropatias Diabéticas/complicações , Intervalo Livre de Doença , Predisposição Genética para Doença , Genótipo , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/complicações , Reação em Cadeia da Polimerase , Polimorfismo Genético , Modelos de Riscos Proporcionais , Receptor para Produtos Finais de Glicação Avançada , Fatores de Risco
3.
Clin Nephrol ; 64(5): 337-42, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16312260

RESUMO

BACKGROUND: The histology and function of the kidney deteriorates with age and progressive renal failure, but the mechanisms involved in renal ageing are not known. In vitro studies suggest that telomere shortening is important in replicative senescence, and is accelerated by stress factors that increase replication. We investigated whether IgA nephropathy, a prototype chronic kidney disease, is associated with localized intrarenal cellular ageing. METHODS: We studied the mean length of terminal restriction fragments (TRF), a measure of average telomere size, in the DNA of peripheral blood mononuclear cells and urinary sediment of 15 patients with IgA nephropathy. RESULTS: The mean TRF lengths in peripheral blood is 7043.8 +/- 1 182.8 base pairs, and in urinary sediment is 6 749.7 +/- 636.5 base pairs. The mean TRF lengths of urinary DNA significantly correlate with the serum creatinine (r = -0.525, p = 0.044) and estimated glomerular filtration rate (GFR) (r = 0.651, p = 0.009). The mean TRF lengths of urinary DNA had an insignificant inverse correlation with patient age (r = -0.364, p = 0.2), and do not correlate with the degree of glomerulosclerosis (r = 0.004, p = 0.9) or tubulointerstitial scarring in renal biopsy (r =-0.032, p = 0.9). After 30 months of follow-up, the rate of decline of estimated GFR has an inverse correlation with the mean TRF lengths of urinary DNA (r = -0.699, p = 0.004). The TRF lengths of peripheral blood DNA do not correlate with any clinical or histological parameter or the rate of renal function decline. CONCLUSIONS: Although this is a pilot study, our observation indicates that the TRF lengths of genomic DNA extracted from urinary sediment is related to the degree of renal impairment. However, a long telomere length of genomic DNA in urinary sediment is associated with a more rapid decline of renal function. Our findings might be relevant to the pathogenesis of progressive renal failure.


Assuntos
DNA/urina , Glomerulonefrite por IGA/genética , Glomerulonefrite por IGA/urina , Rim/citologia , Telômero/genética , Adulto , Feminino , Humanos
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