RESUMEN
AIM: To study association of gene TP53 polymorphic marker Pro72Arg coding synthesis of p53 protein with onset, course and progress of chronic glomerulonephritis (CGN). MATERIAL AND METHODS: We examined 126 patients (63 males and 63 females, mean age 38.8 +/- 13.2 years) with CGN duration 13.0 +/- 9.1 years. When analyzing genetic predisposition to CGN, we compared incidence rate of alleles/genotypes of polymorphic marker Pro72Arg of gene TP53 in CGN patients and 69 controls free of renal disease. CGN clinical features were assessed retrospectively including analysis of nephritis onset, clinical and morphological variants. The course of CGN was analysed by changes in severity of hypertension, persistence of proteinuria > 3 g/day during 6 months and longer, conduction of immunosuppressive therapy and response to it. In analysis of progression rate, doubling of blood creatinine was considered as an end point. We used polymerase chain reaction with analysis of restriction fragment length for identification of alleles of Pro 72Arg polymorphic marker of TP53 gene. RESULTS: Distribution of the genotypes of the above polymorphic marker in CGN patients and in controls did not significantly differ. Depending on Pro allele carriage, CGN patients were divided into two groups: Arg/Arg group (59 carriers of genotype Arg/Arg) and Pro group (63 patients with genotype Arg/Pro and 4 with genotype Pro/Pro). Carriage of Pro allele of gene TP53 was associated with high CGN activity at onset, presence of arteriolosclerosis and IgA deposits in kidney biopsy. Patients with genotype Arg/Arg more frequently developed nephritic syndrome without renal dysfunction syndrome. CONCLUSION: We have discovered association of gene TP53 polymorphic marker Pro72Arg with clinical manifestations of CGN. Carriers of Pro allele more often have signs of active glomerular inflammation and vascular impairment with renal dysfunction while carriers of Arg/Arg genotype more frequently demonstrate isolated nephritic syndrome.
Asunto(s)
Glomerulonefritis/diagnóstico , Glomerulonefritis/genética , Proteína p53 Supresora de Tumor/genética , Adolescente , Adulto , Anciano , Alelos , Sustitución de Aminoácidos , Arginina/genética , Enfermedad Crónica , Progresión de la Enfermedad , Femenino , Marcadores Genéticos , Glomerulonefritis/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Prolina/genética , Adulto JovenRESUMEN
A comparative analysis of allelic and genotype distribution of polymorphic markers Val762Ala and Leu54Phe of ADPRT1 gene encoding poly(ADP-ribose)polymerase I has been performed in chronic glomerulonephritis patients compared to normal controls. This has shown a significant difference in the ADPRTI gene polymorphic marker Val762Ala allelic and genotype frequency distribution between chronic glomerulonephritis patients and healthy controls (according to Fisher's exact test). At the same time the allelic and genotype frequency for a polymorphic marker Leu54Phe distribution did not show significant difference between these groups. Therefore, we have concluded that the ADPRTI gene polymorphic marker Val762Ala is associated with the development of chronic glomerulonephritis in Russian patients of the Moscow region.
Asunto(s)
Glomerulonefritis/genética , Poli(ADP-Ribosa) Polimerasas/genética , Polimorfismo Genético , Adolescente , Adulto , Anciano , Alelos , Niño , Preescolar , Enfermedad Crónica , Femenino , Marcadores Genéticos , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Moscú , Poli(ADP-Ribosa) Polimerasa-1RESUMEN
The distributions of the alleles and genotypes of Polymorphic markers D6S2414 and D6S1271 located among class II MHC genes have been studied in patients with chronic glomerulonephritis (CGN) and healthy donors. Both markers have been found to be associated with the disease. Since these microsatellites are located in the chromosomal region occupied by class II MHC genes, their association with CGN indirectly indicates that class II MHC genes are involved in the development of this pathology.